Molecules

476 KiB

Open AccessReview

Preventive Effects of Catechins on Cardiovascular Disease

by Xiao-Qiang Chen, Ting Hu, Yu Han, Wei Huang, Hai-Bo Yuan, Yun-Tian Zhang, Yu Du and Yong-Wen Jiang

Molecules 2016, 21(12), 1759; https://doi.org/10.3390/molecules21121759 - 21 Dec 2016

Cited by 83 | Viewed by 8071

Abstract

Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the [...] Read more.

Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the prevention and treatment of cardiovascular disorders, and we review the preventive effects of catechins on cardiovascular disease from the following aspects: Regulating lipid metabolism, regulating blood lipid metabolism, vascular endothelial protection, and reducing blood pressure. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

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5641 KiB

Open AccessArticle

Cryptolepine, a Plant Alkaloid, Inhibits the Growth of Non-Melanoma Skin Cancer Cells through Inhibition of Topoisomerase and Induction of DNA Damage

by Harish C. Pal and Santosh K. Katiyar

Molecules 2016, 21(12), 1758; https://doi.org/10.3390/molecules21121758 - 21 Dec 2016

Cited by 46 | Viewed by 7152

Abstract

Topoisomerases have been shown to have roles in cancer progression. Here, we have examined the effect of cryptolepine, a plant alkaloid, on the growth of human non-melanoma skin cancer cells (NMSCC) and underlying mechanism of action. For this purpose SCC-13 and A431 cell [...] Read more.

Topoisomerases have been shown to have roles in cancer progression. Here, we have examined the effect of cryptolepine, a plant alkaloid, on the growth of human non-melanoma skin cancer cells (NMSCC) and underlying mechanism of action. For this purpose SCC-13 and A431 cell lines were used as an in vitro model. Our study reveals that SCC-13 and A431 cells express higher levels as well as activity of topoisomerase (Topo I and Topo II) compared with normal human epidermal keratinocytes. Treatment of NMSCC with cryptolepine (2.5, 5.0 and 7.5 µM) for 24 h resulted in marked decrease in topoisomerase activity, which was associated with substantial DNA damage as detected by the comet assay. Cryptolepine induced DNA damage resulted in: (i) an increase in the phosphorylation of ATM/ATR, BRCA1, Chk1/Chk2 and γH2AX; (ii) activation of p53 signaling cascade, including enhanced protein expressions of p16 and p21; (iii) downregulation of cyclin-dependent kinases, cyclin D1, cyclin A, cyclin E and proteins involved in cell division (e.g., Cdc25a and Cdc25b) leading to cell cycle arrest at S-phase; and (iv) mitochondrial membrane potential was disrupted and cytochrome c released. These changes in NMSCC by cryptolepine resulted in significant reduction in cell viability, colony formation and increase in apoptotic cell death. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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Figure 1
Comparison of basal expression and activity of topoisomerases in non-melanoma skin cancer (NMSC) cell lines, and effect of cryptolepine on topoisomerase in NMSC cells. (A) Molecular structure of cryptolepine, a plant alkaloid; (B) Basal expression of topoisomerases (Topo I and Topo IIα) in various cell lines was determined in total cell lysates using western blot analysis; (C) Topoisomerases containing cell extracts were subjected to the analysis of enzyme activity using topoisomerase activity assay kit, as detailed in Materials and Methods; (D) SCC-13 and A431 cells were treated with various concentrations of cryptolepine (0, 2.5, 5.0, and 7.5 μM) for 24 h, total cell lysates were subjected to western blot analysis for the detection of Topo I and Topo IIα. The numerical value of band density is shown under blot, and the band density of control was arbitrarily selected as 1 and comparison was then made with densitometry values of other treatment groups; (E) Cell extracts containing topoisomerases from different treatment groups were subjected to the analysis of enzyme activity using topoisomerase activity assay kit. Topo = topoisomerase, Sup DNA = Supercoiled DNA, Rel DNA = Relax DNA. Full article ">Figure 2
Treatment of NMSC cells with cryptolepine induces DNA damage which is associated with inhibition of topoisomerase IIα expression and induction of DNA-PK protein expression. (A) Cryptolepine (0, 2.5, 5.0 and 7.5 µM for 24 h) induced DNA damage was determined by comet assay, as described in Materials and Methods; (B) Comet’s tail length was measured using opencomet software. Data are expressed in terms of tail length as mean ± SD, n = 6. Statistical significance versus control, * p < 0.05; ¶ p < 0.01; † p < 0.001; (C) Approximately 5 × 104 SCC-13 or A431 cells/well of four chambered slide were treated with 0, 2.5, 5.0 and 7.5 µM of cryptolepine for 24 h and stained with topoisomerase IIα- and DNA-PK-specific primary antibodies for double staining, as detailed in Materials and methods. After washing with PBS, slides were mounted with vectashield mounting media containing DAPI. Representative photomicrographs are shown. Bar size = 5 µm. Full article ">Figure 3
Treatment of cryptolepine enhances the expressions of DNA damage response mediators and effector cascade in NMSC cells. (A) Cryptolepine treatment enhances expressions of DNA damage response proteins in SCC-13 and A431 cells; and (B) DNA damage effectors in SCC-13 and A431 cells. Cells were treated with cryptolepine (0, 2.5, 5.0 and 7.5 µM) for 24 h. Cell lysates were subjected to western blot analysis for determination of the levels of different protein biomarkers. Blots were developed with chemiluminescence-specific ECL. The numerical value of band density is shown under blot, and the band density of control was arbitrarily selected as 1 and comparison was then made with densitometry values of other treatment groups, as detailed under Materials and Methods. Equal loading of proteins was confirmed by stripping the membranes and probed with β-actin or vinculin. Full article ">Figure 4
Treatment of cryptolepine induces S-phase cell cycle arrest in NMSC cells. (A) Approximately 2 × 105 SCC-13 or A431 cells were treated with different doses of cryptolepine (0, 2.5, 5.0 and 7.5 µM) for 24 h. After harvesting the cells, cells were stained with propidium iodide and analyzed on Accuri Q6 flow cytometer for DNA content in different phases of cell cycle. M3 compartment shows the cells in S-phase; (B) Cell lysates from cryptolepine treated and non-treated controls of SCC-13 and A431 cells were subjected to western blot analysis to determine the effect on expression of cell cycle regulatory proteins. The numerical value of band density is shown under blot, and the band density of control (non-treated group) was arbitrarily selected as 1 and comparison was then made with densitometry values of other treatment groups. Full article ">Figure 5
Cryptolepine treatment stimulates the loss of mitochondrial membrane potential and subsequently release cytochrome c in NMSC cells. (A) SCC-13 or A431 cells were treated with various concentrations of cryptolepine (0, 2.5, 5.0 and 7.5 µM) for 24 h, then double staining was performed using phospho-p53- and cytochrome c specific primary antibodies following the immunohistochemistry protocol as detailed under Materials and Methods. Green color reflects the release of cytochrome c, red color shows the expression of P-p53 and DAPI shows blue. Representative photomicrographs are shown. Bar size = 5 µm; (B) SCC-13 or A431 cells were treated with different doses of cryptolepine (0, 2.5, 5.0 and 7.5 µM) for 24 h. Cells were incubated with rhodamine-123 for 30 min and then harvested for the analysis of mitochondrial membrane potential using Accuri Q6 flow cytometer. M1 compartment indicates percent of cells with intact mitochondrial membrane potential while M2 compartment indicates percent cells with loss of mitochondrial membrane potential. Full article ">Figure 6
Treatment of cryptolepine inhibits cell viability, induces apoptosis and reduced colony formation capacity of NMSC cells. NMSC cells (SCC-13 and A431) and NHEK were treated with different concentrations of cryptolepine (0, 2.5, 5.0 and 7.5 µM) for 24 and 48 h. (A) Cell viability was determined using MTT assay. Experiment was performed in six individual wells of 96 wells plate and cell viability was compared with the control, n = 6. Statistical significance versus control, * p < 0.05; ¶ p < 0.01; † p < 0.001; (B) Cells were treated with various concentrations of cryptolepine (0, 2.5, 5.0 and 7.5 µM) for 24 h. Thereafter, cells were harvested, and incubated with Alexa488 reagents and PI for 30 min, percent apoptotic cell population was analyzed using Accuri Q6 flow cytometer, as described in Materials and Methods; (C) After treatment with cryptolepine (0, 2.5 and 5.0 µM) for 24 h, 500 NMSC cells were allowed to grow in 6-well plates in duplicate for 2 weeks at 37 °C in an incubator. After two weeks, colonies were identified using 0.5% crystal violet. Cell colonies were scanned for photographs, and are seen in blue; (D) Western blot analysis indicates that the levels of Topo IIα was markedly decreased in the NMSC cells after knocked-down of Topo IIα using siRNA kit; (E) Cell viability in SCC-13 and A431 cell lines was significantly decreased (p < 0.001) after knock-down of Topo IIα using siRNA kit compared to the cells treated with control siRNA. Full article ">Figure 7
Schematic representation of cryptolepine-induced effects on non-melanoma skin cancer cells (NMSCC). Cryptolepine inhibits topoisomerase and causes DNA damage in skin cancer cells. Cryptolepine induced DNA damage response leads to activation of ATM/ATR and checkpoint kinases (Chk1/Chk2) resulting in activation of p53 signaling and modulation of cell cycle regulatory proteins. Together, these changes induced by cryptolepine results in cell cycle arrest and ultimately induction of apoptotic cell death of NMSCC. Full article ">

1500 KiB

Open AccessArticle

Pharmacological Properties of Riparin IV in Models of Pain and Inflammation

by Olívia Azevêdo Nascimento, Renan Fernandes do Espírito-Santo, Luíza Carolina França Opretzka, José Maria Barbosa-Filho, Stanley Juan Chavez Gutierrez, Cristiane Flora Villarreal and Milena Botelho Pereira Soares

Molecules 2016, 21(12), 1757; https://doi.org/10.3390/molecules21121757 - 21 Dec 2016

Cited by 20 | Viewed by 5539

Abstract

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory [...] Read more.

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and IV (1.56–100 mg/kg; ip) produced dose-related antinociceptive effects in the formalin test, exhibiting ED₅₀ values of 22.93, 114.2, 31.05 and 6.63 mg/kg, respectively. Taking the greater potency as steering parameter, riparin IV was further investigated. Riparin IV did not produce antinociceptive effect on the tail flick, suggesting that its antinociception is not a centrally-mediated action. In fact, riparin IV (1.56–25 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on the complete Freund’s adjuvant (CFA)-induced paw inflammation in mice. During CFA-induced inflammation, riparin IV did not modulate either the production of cytokines, TNF-α and IL-10, or COX-2 mRNA expression. On the other hand, riparin IV decreased the PGE₂ levels in the inflamed paw. In in vitro assays, riparin IV did not exhibit suppressive activities in activated macrophages. These results indicate, for the first time, that riparin IV induces antinociceptive and anti-inflammatory effects, possibly through the inhibition of prostanoid production. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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7885 KiB

Open AccessArticle

Inhibition of Hypoxia-Induced Retinal Angiogenesis by Specnuezhenide, an Effective Constituent of Ligustrum lucidum Ait., through Suppression of the HIF-1α/VEGF Signaling Pathway

by Jianming Wu, Xiao Ke, Wei Fu, Xiaoping Gao, Hongcheng Zhang, Wei Wang, Na Ma, Manxi Zhao, Xiaofeng Hao and Zhirong Zhang

Molecules 2016, 21(12), 1756; https://doi.org/10.3390/molecules21121756 - 21 Dec 2016

Cited by 42 | Viewed by 7654

Abstract

Specnuezhenide (SPN), one of the main ingredients of Chinese medicine “Nü-zhen-zi”, has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion [...] Read more.

Specnuezhenide (SPN), one of the main ingredients of Chinese medicine “Nü-zhen-zi”, has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion model of human acute retinal pigment epithelial-19 (ARPE-19) cells by exposure of 150 μM CoCl₂ to the cells and determined the VEGFA concentrations, the mRNA expressions of VEGFA, hypoxia inducible factor-1α (HIF-1α) & prolyl hydroxylases 2 (PHD-2), and the protein expressions of HIF-1α and PHD-2 after treatment of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1, 1.0 μg/mL) or SPN (0.2, 1.0 and 5.0 μg/mL). Furthermore, rat pups with retinopathy were treated with SPN (5.0 and 10.0 mg/kg) in an 80% oxygen atmosphere and the retinal avascular areas were assessed through visualization using infusion of ADPase and H&E stains. The results showed that SPN inhibited VEGFA secretion by ARPE-19 cells under hypoxia condition, down-regulated the mRNA expressions of VEGFA and PHD-2 slightly, and the protein expressions of VEGFA, HIF-1α and PHD-2 significantly in vitro. SPN also prevented hypoxia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy in vivo. These results indicate that SPN ameliorates retinal neovascularization through inhibition of HIF-1α/VEGF signaling pathway. Therefore, SPN has the potential to be developed as an agent for the prevention and treatment of diabetic retinopathy. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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1013 KiB

Open AccessArticle

Polyphenol Composition, Antioxidant Activity and Cytotoxicity of Seeds from Two Underexploited Wild Licania Species: L. rigida and L. tomentosa

by Igor Parra Pessoa, José Joaquim Lopes Neto, Thiago Silva de Almeida, Davi Felipe Farias, Leonardo Rogério Vieira, Jackeline Lima de Medeiros, Aline Augusti Boligon, Ad Peijnenburg, Ivan Castelar and Ana Fontenele Urano Carvalho

Molecules 2016, 21(12), 1755; https://doi.org/10.3390/molecules21121755 - 21 Dec 2016

Cited by 15 | Viewed by 6997

Abstract

Studies have shown the benefit of antioxidants in the prevention or treatment of human diseases and promoted a growing interest in new sources of plant antioxidants for pharmacological use. This study aimed to add value to two underexploited wild plant species (Licania [...] Read more.

Studies have shown the benefit of antioxidants in the prevention or treatment of human diseases and promoted a growing interest in new sources of plant antioxidants for pharmacological use. This study aimed to add value to two underexploited wild plant species (Licania rigida) and L. tomentosa) from Brazilian flora. Thus, the phenolic compounds profile of their seed ethanol extract and derived fractions were elucidated by HPLC, the antioxidant capacity was assessed by in vitro chemical tests and the cytotoxicity determined using the human carcinoma cell lines MCF-7 and Caco-2. Eleven phenolic compounds were identified in the extracts of each species. The extracts and fractions showed excellent antioxidant activity in the DPPH assay (SC₅₀, ranging from 9.15 to 248.8 µg/mL). The aqueous fraction of L. rigida seeds was most effective in preventing lipid peroxidation under basal conditions (IC₅₀ 60.80 µg/mL) whereas, in the presence of stress inducer, the methanolic fraction of L. tomentosa performed best (IC₅₀ 8.55 µg/mL). None of the samples showed iron chelating capacity. Ethanolic seed extracts of both species did not reveal any cytotoxicity against MCF-7 and Caco-2 cells. Both plant species showed a promising phenolic profile with potent antioxidant capacity and deserve attention to be sustainably explored. Full article

(This article belongs to the Section Natural Products Chemistry)

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High performance liquid chromatography phenolics and flavonoids profile of L. tomentosa ethanolic extract (a) and L. rigida ethanolic extract (b). Gallic acid (peak 1), catechin (peak 2), chlorogenic acid (peak 3), caffeic acid (peak 4), epicatechin (peak 5), ellagic acid (peak 6), rutin (peak 7), quercitrin (peak 8), quercetin (peak 9), kaempferol (peak 10) and kaempferol glycoside (peak 11). Full article ">Figure 2
Iron chelating activity of Licania rigida (a) and L. tomentosa (b) seeds ethanolic extract and their fractions based on o-phenantroline method. Absorbance was recorded at 510 nm and percent complexation was calculated with respect to control (determined in the absence of samples and EDTA). LrEE = L. rigida ethanolic extract; LrMF = L. rigida methanolic fraction; LrEAF = L. rigida ethyl acetate fraction; LrAF = L. rigida aqueous fraction LtEE = L. tomentosa ethanolic extract; LtMF = L. tomentosa methanolic fraction; LtEAF = L. tomentosa ethyl acetate fraction; LtAF = L. tomentosa aqueous fraction; LtCF = L. tomentosa chloroform fraction; EDTA = Ethylenediamine tetraacetic acid. * Significant difference between EDTA control and all the samples in A and B (p < 0.05). ** Significant difference between LtMF/LtAF and other samples in B (p < 0.05). Full article ">Figure 3
Cell viability of the human breast adenocarcinoma cell line MCF-7 upon 24 h exposure to ethanolic seeds extracts of Licania tomentosa (A); L. rigida (B); quercetin (C) and gallic acid (D). DMSO, dimethyl sulfoxide; DMEM: Dulbecco's Modified Eagle's Medium; LrEE: L. rigida ethanolic extract; LtEE: L. tomentosa ethanolic extract. Full article ">Figure 4
Cell viability of the human colon adenocarcinoma cell line Caco-2 upon 24 h exposure to ethanolic seeds extracts of Licania rigida (A); L. tomentosa (B); quercetin (C) and gallic acid (D). DMSO, dimethyl sulfoxide; DMEM, Dulbecco's Modified Eagle's Medium; LrEE, L. rigida ethanolic extract; LtEE, L. tomentosa ethanolic extract. Full article ">

1648 KiB

Open AccessArticle

Chemical Fingerprint Analysis and Quantitative Analysis of Rosa rugosa by UPLC-DAD

by Sanawar Mansur, Rahima Abdulla, Amatjan Ayupbec and Haji Akbar Aisa

Molecules 2016, 21(12), 1754; https://doi.org/10.3390/molecules21121754 - 21 Dec 2016

Cited by 13 | Viewed by 6543

Abstract

A method based on ultra performance liquid chromatography with a diode array detector (UPLC-DAD) was developed for quantitative analysis of five active compounds and chemical fingerprint analysis of Rosa rugosa. Ten batches of R. rugosa collected from different plantations in the Xinjiang [...] Read more.

A method based on ultra performance liquid chromatography with a diode array detector (UPLC-DAD) was developed for quantitative analysis of five active compounds and chemical fingerprint analysis of Rosa rugosa. Ten batches of R. rugosa collected from different plantations in the Xinjiang region of China were used to establish the fingerprint. The feasibility and advantages of the used UPLC fingerprint were verified for its similarity evaluation by systematically comparing chromatograms with professional analytical software recommended by State Food and Drug Administration (SFDA) of China. In quantitative analysis, the five compounds showed good regression (R² = 0.9995) within the test ranges, and the recovery of the method was in the range of 94.2%–103.8%. The similarities of liquid chromatography fingerprints of 10 batches of R. rugosa were more than 0.981. The developed UPLC fingerprint method is simple, reliable, and validated for the quality control and identification of R. rugosa. Additionally, simultaneous quantification of five major bioactive ingredients in the R. rugosa samples was conducted to interpret the consistency of the quality test. The results indicated that the UPLC fingerprint, as a characteristic distinguishing method combining similarity evaluation and quantification analysis, can be successfully used to assess the quality and to identify the authenticity of R. rugosa. Full article

(This article belongs to the Section Natural Products Chemistry)

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1618 KiB

Open AccessReview

Sulfur Atom in its Bound State Is a Unique Element Involved in Physiological Functions in Mammals

by Shin Koike and Yuki Ogasawara

Molecules 2016, 21(12), 1753; https://doi.org/10.3390/molecules21121753 - 21 Dec 2016

Cited by 31 | Viewed by 8208

Abstract

It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term “sulfane sulfur” sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article, [...] Read more.

It was in the 1950s that the term polysulfide or persulfide was introduced in biological studies. The unfamiliar term “sulfane sulfur” sometimes appeared in papers published in the 1970s, and was defined in the review article by Westley in 1983. In the article, sulfane sulfur is described as sulfur atoms that are covalently bound only with sulfur atoms, and as this explanation was somewhat difficult to comprehend, it was not generally accepted. Thus, in the early 1990s, we redefined these sulfur species as “bound sulfur”, which easily converts to hydrogen sulfide on reduction with a thiol reducing agent. In other words, bound sulfur refers to a sulfur atom that exists in a zero to divalent form (0 to −2). The first part of this review focuses on the fluorescent derivatization HPLC method—which we developed for measurement of bound sulfur—and explains the distribution of bound sulfur and the hydrogen sulfide-producing ability of various tissues, as clarified by this method. Next, we discuss diverse physiological functions and involvement of polysulfide, a typical type of bound sulfur, in the redox regulation system. Additionally, we also address its possible physiological role in the central nervous system, based on its action of scavenging reactive carbonyl compounds. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

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151 KiB

Open AccessEditorial

Recent Advances in Olefin Metathesis

by Georgios C. Vougioukalakis

Molecules 2016, 21(12), 1751; https://doi.org/10.3390/molecules21121751 - 21 Dec 2016

Cited by 2 | Viewed by 4523

Abstract

Olefin metathesis is one of the most significant developments of the last 20 years in the fields of organic chemistry, polymers synthesis, and materials science [1–7]. [...]
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(This article belongs to the Special Issue Olefin Metathesis)

1331 KiB

Open AccessArticle

New Iridoid Glucosides from Caryopteris incana (Thunb.) Miq. and Their α-Glucosidase Inhibitory Activities

by Xu-Dong Mao, Gui-Xin Chou, Sen-Miao Zhao and Cheng-Gang Zhang

Molecules 2016, 21(12), 1749; https://doi.org/10.3390/molecules21121749 - 21 Dec 2016

Cited by 8 | Viewed by 5163

Abstract

In our continued investigations of the plant Caryopteris incana, five new iridoid glucosides 1–5, including two cis-trans-isomers, 3 and 4, along with six known compounds 6–11, were isolated from the n-butyl alcohol ( [...] Read more.

In our continued investigations of the plant Caryopteris incana, five new iridoid glucosides 1–5, including two cis-trans-isomers, 3 and 4, along with six known compounds 6–11, were isolated from the n-butyl alcohol (n-BuOH) soluble fraction of whole dried material of Caryopteris incana. Their structures were established by a combination of spectroscopic techniques, including 1D and 2D NMR and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Furthermore, all isolates were evaluated for their yeast α-glucosidase inhibitory effects. Among these compounds, 4–8 and 10 exhibited potent inhibition of α-glucosidase. Full article

(This article belongs to the Section Natural Products Chemistry)

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2661 KiB

Open AccessArticle

Hypervalent Iodine(III)-Induced Domino Oxidative Cyclization for the Synthesis of Cyclopenta[b]furans

by Mei-Huey Lin, Yu-Chun Chen, Shih-Hao Chiu, Yun-Fan Chen and Tsung-Hsun Chuang

Molecules 2016, 21(12), 1713; https://doi.org/10.3390/molecules21121713 - 21 Dec 2016

Cited by 2 | Viewed by 5056

Abstract

A new strategy for cyclopenta[b]furan synthesis mediated by hypervalent iodine(III) has been described. The approach employs diacetoxyiodobenzene-induced initial dehydrogenation to a putative trienone intermediate and triggered sequential cycloisomerization to form the cyclo-penta[b]furan targets. Full article

(This article belongs to the Special Issue Hypervalent Iodine Chemistry)

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562 KiB

Open AccessArticle

Comparative Study on the Characteristics of Weissella cibaria CMU and Probiotic Strains for Oral Care

by Hye-Jin Jang, Mi-Sun Kang, Sung-Hun Yi, Ji-Young Hong and Sang-Pil Hong

Molecules 2016, 21(12), 1752; https://doi.org/10.3390/molecules21121752 - 20 Dec 2016

Cited by 46 | Viewed by 7849

Abstract

Probiotics have been demonstrated as a new paradigm to substitute antibiotic treatment for dental caries, gingivitis, and chronic periodontitis. The present work was conducted to compare the characteristics of oral care probiotics: Weissella cibaria CMU (Chonnam Medical University) and four commercial probiotic strains. [...] Read more.

Probiotics have been demonstrated as a new paradigm to substitute antibiotic treatment for dental caries, gingivitis, and chronic periodontitis. The present work was conducted to compare the characteristics of oral care probiotics: Weissella cibaria CMU (Chonnam Medical University) and four commercial probiotic strains. Survival rates under poor oral conditions, acid production, hydrogen peroxide production, as well as inhibition of biofilm formation, coaggregation, antibacterial activity, and inhibition of volatile sulfur compounds were evaluated. The viability of W. cibaria CMU was not affected by treatment of 100 mg/L lysozyme for 90 min and 1 mM hydrogen peroxide for 6 h. Interestingly, W. cibaria produced less acid and more hydrogen peroxide than the other four probiotics. W. cibaria inhibited biofilm formation by Streptococcus mutans at lower concentrations (S. mutans/CMU = 8) and efficiently coaggregated with Fusobacterium nucleatum. W. cibaria CMU and two commercial probiotics, including Lactobacillus salivarius and Lactobacillus reuteri, showed high antibacterial activities (>97%) against cariogens (S. mutans and Streptococcus sobrinus), and against periodontopathogens (F. nucleatum and Porphyromonas gingivalis). All of the lactic acid bacterial strains in this study significantly reduced levels of hydrogen sulfide and methyl mercaptan produced by F. nucleatum and P. gingivalis (p < 0.05). These results suggest that W. cibaria CMU is applicable as an oral care probiotic. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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145 KiB

Open AccessEditorial

Natural Products in Anti-Obesity Therapy

by Filomena Conforti and Min-Hsiung Pan

Molecules 2016, 21(12), 1750; https://doi.org/10.3390/molecules21121750 - 20 Dec 2016

Cited by 14 | Viewed by 5066

Abstract

Obesity is regulated by genetic, endocrine, metabolic, neurological, pharmacological, environmental, and nutritional factors. [...]
Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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Open AccessReview

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

by Caroline Coisne, Sébastien Tilloy, Eric Monflier, Daniel Wils, Laurence Fenart and Fabien Gosselet

Molecules 2016, 21(12), 1748; https://doi.org/10.3390/molecules21121748 - 20 Dec 2016

Cited by 94 | Viewed by 12774

Abstract

Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the [...] Read more.

Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE^® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer’s, Parkinson’s and Huntington’s diseases are currently on-going. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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Figure 1
Impact of β-CDs on reverse cholesterol transfer (RCT) and in atherosclerosis. As showed in <a href="#molecules-21-01748-t002" class="html-table">Table 2</a>, β-CD family shows promising therapeutic properties in atherosclerosis field. β-CDs are able to extract cholesterol and phospholipids from cell membrane (1) resulting in the decrease of lipid intracellular pools (2). This process leads to an activation of the liver X signaling (LXR) pathway (3) which in turn regulates the expression of ABCA1 and ABCG1 (4). As a consequence, the formation and lipidation of HDL particles are modified (5 and 6). In vitro, lipid extraction by CDs provokes a down-regulation of ABCA1 and ABCG1 expression and a decrease in the free cholesterol transfer to ApoA-I [<a href="#B12-molecules-21-01748" class="html-bibr">12</a>,<a href="#B13-molecules-21-01748" class="html-bibr">13</a>]. However, in tissues from ApoE−/− animals or when cells are cholesterol-loaded in vitro, lipid extraction induces an increase in the cholesterol efflux mediated by the up-regulation of these ABC transporters [<a href="#B13-molecules-21-01748" class="html-bibr">13</a>] (7). Noteworthy, in brain, apolipoprotein E remains the main cholesterol acceptor forming HDL. CD-mediated activation of LXR pathway inhibits inflammatory response (8) [<a href="#B11-molecules-21-01748" class="html-bibr">11</a>,<a href="#B13-molecules-21-01748" class="html-bibr">13</a>]. In addition, CDs promote atherosclerotic size plaque reduction in vivo (9) by a HDL-independent mechanism which remains unclear [<a href="#B11-molecules-21-01748" class="html-bibr">11</a>,<a href="#B13-molecules-21-01748" class="html-bibr">13</a>]. HDL: High density lipoproteins; LXR: Liver X receptor; ApoA-I/ApoE: Apolipoproteins A-I and E. Full article ">Figure 2
Molecular mechanisms mediated by β-CDs in Alzheimer’s, Parkinson’s, Hugtington’s, Niemann-Pick Type C diseases. Niemann-Pick Type C disease is characterized by intracellular accumulation of unesterified cholesterol and glycosphingolipids. Alzheimer’s, Parkinson’s and Huntington’s diseases are charaterized by abnormal aggregation of peptides leading to the neurodegenerative processes. β-CD family acts at several levels and shows beneficial effects in these neurodegenerative diseases. Full article ">

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Open AccessReview

A Review of the Botany, Phytochemistry, Pharmacology and Toxicology of Rubiae Radix et Rhizoma

by Mingqiu Shan, Sheng Yu, Hui Yan, Peidong Chen, Li Zhang and Anwei Ding

Molecules 2016, 21(12), 1747; https://doi.org/10.3390/molecules21121747 - 20 Dec 2016

Cited by 39 | Viewed by 8717

Abstract

Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis, [...] Read more.

Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis, epistaxis, flooding, spotting, traumatic bleeding, amenorrhea caused by obstruction, joint impediment pain, swelling and pain caused by injuries from falls. In addition, it is a kind of pigment utilized as a food additive and a dye for wool or fiber. This review mainly concentrates on studies of the botany, phytochemistry, pharmacology and toxicology of this Traditional Chinese Medicine. The phytochemical evidences indicated that over a hundred chemical components have been found and isolated from the medicine, such as anthraquinones, naphthoquinones, triterpenoids, cyclic hexapeptides and others. These components are considered responsible for the various bioactivities of the herbal drug, including anti-oxidation, anti-inflammation, immunomodulation, antitumor, effects on coagulation-fibrinolysis system, neuroprotection and other effects. Additionally, based on these existing results, we also propose some interesting future research directions. Consequently, this review should help us to more comprehensively understand and to more fully utilize the herbal medicine Rubiae Radix et Rhizoma. Full article

(This article belongs to the Collection Herbal Medicine Research)

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Open AccessArticle

Effects of Quercetin in a Rat Model of Hemorrhagic Traumatic Shock and Reperfusion

by Virginia Chamorro, Rachele Pandolfi, Laura Moreno, Bianca Barreira, Andrea Martínez-Ramas, Daniel Morales-Cano, Jesús Ruiz-Cabello, José Angel Lorente, Juan Duarte, Ángel Cogolludo, José Luis Alvarez-Sala and Francisco Perez-Vizcaino

Molecules 2016, 21(12), 1739; https://doi.org/10.3390/molecules21121739 - 20 Dec 2016

Cited by 11 | Viewed by 5676

Abstract

Background: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. Methods: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min [...] Read more.

Background: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. Methods: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min (trauma), hemorrhagic shock (blood withdrawal to reduce the mean arterial pressure to 35 mmHg) for 75 min and resuscitation by re-infusion of all the shed blood plus lactate Ringer for 90 min. Intravenous quercetin (50 mg/kg) or vehicle were administered during resuscitation. Results: There was a trend for increased survival 84.6% (11/13) in the treated group vs. the shock group 68.4% (13/19, p > 0.05 Kaplan–Meier). Quercetin fully prevented the development of lung edema. The activity of aSMase was increased in the shock group compared to the sham group and the quercetin prevented this effect. However, other inflammatory markers such as myeloperoxidase activity, interleukin-6 in plasma or bronchoalveolar fluid were similar in the sham and shock groups. We found no bacterial DNA in plasma in these animals. Conclusions: Quercetin partially prevented the changes in blood pressure and lung injury in shock associated to hemorrhage and reperfusion. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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Figure 1
Kaplan–Meier survival analysis during the reperfusion period. Anaesthetized animals were submitted to shock and at time 90 they were reperfused with blood plus lactate Ringer and with vehicle or quercetin, and followed for an additional period of 90 min. * p < 0.05 vs. sham (log-rank test). Full article ">Figure 2
Changes in (A) mean arterial blood pressure and (B) heart rate in the three experimental groups. Rats were subjected to laparotomy followed by controlled hypotension (shock phase) and then by resuscitation with lactate Ringer solution, shed blood and the quercetin or vehicle. Data are shown as the mean ± S.E.M. * p < 0.05 and ** p < 0.01 vs. sham group during reperfusion (Dunnett’s test). Full article ">Figure 3
aSMase activity. Measurements were made in lung homogenate for a total time of 30 min expressed as nmol/min/mL. * p < 0.05 vs. sham group. Box-and-whisker plot showing medians with interquartile range and minimum and maximum values. Full article ">Figure 4
Arterial blood gases. (A) Values of pH; (B) carbon dioxide partial pressure (pCO2); (C) excess base; (D) bicarbonate (HCO3−); (E) total carbon dioxide concentration (TCO2); (F) arterial oxygen saturation (SO2) and (G) arterial oxygen partial pressure (pO2) in the sham, shock and shock + quercetin at 180 min (at the end of reperfusion). Box-and-whisker plot showing medians with interquartile range and minimum and maximum values. * p < 0.05 and ** p < 0.01 vs. sham group. Full article ">Figure 5
Markers of inflammation and vascular permeability: (A) Edema (wet to dry weight ratio); (B) proteins in Bronchoalveolar Lavage Fluid (BALF); (C) IgM BALF/plasma ratio (D) cells in BALF; (E) Myeloperoxidase (MPO) activity and (F) IL-6 in BALF measured at the end of reperfusion. Box-and-whisker plot showing medians with interquartile range and minimum and maximum values in each group. * p < 0.05, ** p < 0.01 and *** p < 0.005 vs. sham group. Full article ">Figure 5 Cont.
Markers of inflammation and vascular permeability: (A) Edema (wet to dry weight ratio); (B) proteins in Bronchoalveolar Lavage Fluid (BALF); (C) IgM BALF/plasma ratio (D) cells in BALF; (E) Myeloperoxidase (MPO) activity and (F) IL-6 in BALF measured at the end of reperfusion. Box-and-whisker plot showing medians with interquartile range and minimum and maximum values in each group. * p < 0.05, ** p < 0.01 and *** p < 0.005 vs. sham group. Full article ">

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Open AccessReview

Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment

by Chendi Ding, Ling Tong, Jing Feng and Jiajun Fu

Molecules 2016, 21(12), 1715; https://doi.org/10.3390/molecules21121715 - 20 Dec 2016

Cited by 121 | Viewed by 13267

Abstract

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can [...] Read more.

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs), quantum dots (QDs) and carbon nanotubes (CNTs). The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules) and extrinsic (temperature, light irradiation, magnetic field and ultrasound) ones. Clinical applications of DDS, future challenges and perspectives are also mentioned. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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Open AccessArticle

Targeting Cancer Stem Cells with Novel 4-(4-Substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thiones

by Mashooq Ahmad Bhat, Abdullah Al-Dhfyan and Mohamed A. Al-Omar

Molecules 2016, 21(12), 1746; https://doi.org/10.3390/molecules21121746 - 19 Dec 2016

Cited by 24 | Viewed by 5986

Abstract

Novel 4-(4-substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thione derivatives (DHP 1–9) were designed, synthesized, characterized and evaluated for antitumor activity against cancer stem cells. The compounds were synthesized in one pot. Enaminones E1 and E2 were reacted with substituted benzaldehydes and urea/thiourea [...] Read more.

Novel 4-(4-substituted phenyl)-5-(3,4,5-trimethoxy/3,4-dimethoxy)-benzoyl-3,4-dihydropyrimidine-2(1H)-one/thione derivatives (DHP 1–9) were designed, synthesized, characterized and evaluated for antitumor activity against cancer stem cells. The compounds were synthesized in one pot. Enaminones E1 and E2 were reacted with substituted benzaldehydes and urea/thiourea in the presence of glacial acetic acid. The synthesized compounds were characterized by spectral analysis. The compounds were screened in vitro against colon cancer cell line (LOVO) colon cancer stem cells. Most of the compounds were found to be active against side population cancer stem cells with an inhibition of >50% at a 10 μM concentration. Compounds DHP-1, DHP-7 and DHP-9 were found to be inactive. Compound DHP-5 exhibited an in vitro anti-proliferative effect and arrested cancer cells at the Gap 2 phase (G2) checkpoint and demonstrated an inhibitory effect on tumor growth for a LOVO xenograft in a nude mouse experiment. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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Full article ">Figure 1
Dihydropyrimidine derivatives demonstrating anticancer activity. Full article ">Figure 2
Lead compound Monstrol-97 and newly synthesized compounds (DHP 1–9). Full article ">Figure 3
Scatter plot showing results of side population analyses of tumor-derived cells of LOVO untreated, treated with DHP-1, DHP-4, DHP-5 and DHP-6. Furthermore, compound DHP-5 exhibit an in vitro anti-proliferative effect and arrested cancer cells at the G2 checkpoint (<a href="#molecules-21-01746-f004" class="html-fig">Figure 4</a>). Blue color represents the percentage of cancer stem cells and red color represents the percentage of remaining cells other than cancer stem cells. Full article ">Figure 4
Compound DHP-5 arrested cancer cells at G2 checkpoint. Full article ">Figure 5
Scatter plot showing results of side population analyses of tumor-derived cells of the LOVO xenograft that were untreated, treated with side population inhibitor reference drug Verapamil (200 μM) and with DHP-5 (50 μM). Full article ">Figure 6
Graph showing tumor growth record of LOVO (colon cancer xenograft) in untreated mice group (red line) and DHP-5–treated (50 mg/kg) mice group (blue line). Full article ">Scheme 1
Synthetic route of compounds (DHP 1–9). Full article ">

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Open AccessArticle

Characterization of Fractional Polysaccharides from Gleditsia sinensis and Gleditsia microphylla Gums

by Yantao Liu, Zhenglong Xu, Weian Zhang, Jiufang Duan, Jianxin Jiang and Dafeng Sun

Molecules 2016, 21(12), 1745; https://doi.org/10.3390/molecules21121745 - 19 Dec 2016

Cited by 20 | Viewed by 5584

Abstract

The seeds of Gleditsia sinensis and Gleditsia microphylla, widespread in China, are an important source of galactomannans. G. sinensis gum (GSG) and G. microphylla gum (GMG) were purified and precipitated using different concentrations of ethanol and isopropanol. The GSG and GMG, precipitated [...] Read more.

The seeds of Gleditsia sinensis and Gleditsia microphylla, widespread in China, are an important source of galactomannans. G. sinensis gum (GSG) and G. microphylla gum (GMG) were purified and precipitated using different concentrations of ethanol and isopropanol. The GSG and GMG, precipitated in different stages, presented different characteristics, including polymer recovery, mannose/galactose ratio, chemical composition, molecular weight, and morphological appearance. The galactomannan recovery of GSG and GMG in 33.3% ethanol was 81.7% and 82.5%, respectively, while that in 28.8% isopropanol was 81.3% and 82.9%, respectively. To achieve similar precipitation efficiency, the amount of isopropanol should be lower than that of ethanol because of the lower dielectric constant of isopropanol (20 vs. 25 for ethanol). The precipitation behavior of galactomannans in polar organic solvents was dependent on the molecular structures and properties of the solvent. A higher mannose/galactose ratio and a higher molecular weight was obtained in a lower concentration of alcohols. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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Open AccessArticle

Combined Use of S. pombe and L. thermotolerans in Winemaking. Beneficial Effects Determined Through the Study of Wines’ Analytical Characteristics

by Ángel Benito, Fernando Calderón and Santiago Benito

Molecules 2016, 21(12), 1744; https://doi.org/10.3390/molecules21121744 - 18 Dec 2016

Cited by 56 | Viewed by 6597

Abstract

The most common way to produce red wine is through the use of Saccharomyces cerevisiae strains for alcoholic fermentation and lactic acid bacteria for malolactic fermentation. This traditional winemaking methodology produces microbiologically stable red wines. However, under specific conditions off-flavours can occur, wine [...] Read more.

The most common way to produce red wine is through the use of Saccharomyces cerevisiae strains for alcoholic fermentation and lactic acid bacteria for malolactic fermentation. This traditional winemaking methodology produces microbiologically stable red wines. However, under specific conditions off-flavours can occur, wine quality can suffer and human health problems are possible, especially after the second fermentation by the lactic acid bacteria. In warm countries, problems during the malolactic fermentation arise because of the high pH of the must, which makes it very difficult to properly control the process. Under such conditions, wines with high acetic acid and histamine concentrations are commonly produced. This study investigates a recent red
wine-making technology that uses a combination of Lachancea thermotolerans and Schizosaccharomyces pombe as an alternative to the conventional malolactic fermentation. This work studies new parameters such as aroma compounds, amino acids, ethanol index and sensory evaluation. Schizosaccharomyces pombe totally consumes malic acid while Lachancea thermotolerans produces lactic acid, avoiding excessive deacidification of musts with low acidity in warm viticulture areas. This methodology also reduces the malolactic fermentation hazards in wines with low acidity. The main products are wines that contain less acetic acid, less biogenic amines and precursors and less ethyl carbamate precursors than the traditional wines produced via conventional fermentation techniques. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Chemical Basis of the Fungicidal Activity of Tobacco Extracts against Valsa mali

by Chemical Basis of the Fungicidal Activity of Tobacco Extracts against Valsa mali Suzhen Duan, Yongmei Du, Xiaodong Hou, Ning Yan, Weijie Dong, Xinxin Mao and Zhongfeng Zhang

Molecules 2016, 21(12), 1743; https://doi.org/10.3390/molecules21121743 - 18 Dec 2016

Cited by 32 | Viewed by 6097

Abstract

Under pressure from social criticism and an unclear future, tobacco researchers have begun to seek alternative uses for the product. Here, we present our study on isolating tobacco compounds with fungicidal activity, which could be used as plant-derived pesticides. Using
Valsa mali as [...] Read more.

Under pressure from social criticism and an unclear future, tobacco researchers have begun to seek alternative uses for the product. Here, we present our study on isolating tobacco compounds with fungicidal activity, which could be used as plant-derived pesticides. Using
Valsa mali as the target fungus, agar plate tests were conducted to evaluate the fungicidal activity of various tobacco extracts, including tobacco leaves extracts prepared with different solvents, extracts of different tobacco cultivars, and samples from different tobacco organs. Fungal growth morphology was used as the criterion to evaluate the fungicidal activity of tobacco extracts. Correlation analyses between the fungicidal activities and the chemical components of tobacco extracts indicated the major chemical constituents with fungicidal activity. Then, the active compounds were isolated and their effects on the ultra-microstructures of V. mali was analyzed using scanning- and transmission-electron microscopy. The results suggested that tobacco extracts prepared with solvents of weaker polarity had higher fungicidal activity, and the inhibitory activity of tobacco extracts against V. mali was also cultivar dependent. Furthermore, the fungicidal effects of tobacco flower extracts were higher than those of the leaf extracts. Chemical analysis indicated that cembranoids were the main fungicidal substances, which act by destroying the endometrial structure of the fungus. Tobacco cembranoids at 80 μg/mL could completely inhibit the growth of V. mali, with an EC₅₀ value of 13.18 μg/mL. Our study therefore suggests that tobacco leaves and inflorescences are excellent plant resources for the biological control of V. mali. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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Figure 1
Inhibitory rate against V. mali and the concentration of terpenes of tobacco leaf extracts obtained using different solvents. Columns with different letters represent significantly different extraction solvents according to Duncan’s multiple range tests at p < 0.05. Full article ">Figure 2
Inhibitory rate against V. mali and the concentration of terpenes in different tobacco variety extracts. Columns with different letters represent varieties with significantly different values according to Duncan’s multiple range tests at p < 0.05. Full article ">Figure 3
Inhibitory rate against V. mali and the concentration of terpenes in tobacco flower and leaf n-hexane extracts. Columns with different letters represent organs with significantly different values according to Duncan’s multiple range tests at p < 0.05. Full article ">Figure 4
Total ion chromatogram of the tobacco cembranoids extract. Peaks 1, 2, 3, and 4 represent tobacco cembranoids. Full article ">Figure 5
Inhibitory effect of 95% ethanol (A) and tobacco cembranoids extract (B) on V. mali. Full article ">Figure 6
Ergosterol content of untreated and treated V. mali hyphal cell membranes. Peak 1: The content of ergosterol in membranes treated with 40 μg/mL (working concentration) tobacco cembranoids extract; Peak 2: Ergosterol content following 20 μg/mL (working concentration) treatment; Peak 3: Ergosterol content following treatment 95% ethanol (control). Full article ">Figure 7
Scanning electron microscopy images of untreated and treated V. mali hyphal structure. The untreated hypha appeared round and plump, with structural integrity. (A) 800×; (C) 3000×. After treatment with 40 μg/mL (working concentration) cembranoids extract, the hypha was deformed, showing adhesion and obvious septa. (B) 800×; (D) 3000×. Full article ">Figure 8
Transmission electron microscopy images of untreated and treated V. mali hyphal structures (× 10 k). (A) Horizontal and (C) vertical sections of untreated hyphal structures show regular, uniform cytoplasm; (B) Horizontal and (D) vertical sections of structures following 40 μg/mL (working concentration) cembranoids extract treatment. It can be observed that the cell wall became distorted, the plasma membrane was unevenly thickened, and the intracellular composition was disordered. Full article ">

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Open AccessArticle

Antimicrobial Activity and Urease Inhibition of Schiff Bases Derived from Isoniazid and Fluorinated Benzaldehydes and of Their Copper(II) Complexes

by Ladislav Habala, Samuel Varényi, Andrea Bilková, Peter Herich, Jindra Valentová, Jozef Kožíšek and Ferdinand Devínsky

Molecules 2016, 21(12), 1742; https://doi.org/10.3390/molecules21121742 - 17 Dec 2016

Cited by 28 | Viewed by 7724

Abstract

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. [...] Read more.

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. Also, four copper(II) complexes of these Schiff bases were synthesized. The prepared compounds were evaluated for their antimicrobial activity and urease inhibition. Two of the Schiff bases exerted activity against C. albicans. All copper(II) complexes showed excellent inhibitory properties against jack bean urease, considerably better than that of the standard inhibitor acetohydroxamic acid. Full article

(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)

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Full article ">Figure 1
The molecular structure of ligands (L1–L4), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. Full article ">Figure 2
The crystal packing of ligand L1, viewed along the b axis. Red dashed lines indicate hydrogen interactions. Full article ">Figure 3
The crystal packing of ligand L2, viewed along the b axis. Red dashed lines indicate hydrogen interaction. Full article ">Figure 4
The crystal packing of ligand L3, viewed along the b axis. Red dashed lines indicate hydrogen interactions. Full article ">Figure 5
The crystal packing of ligand L4, viewed along the b axis. Red dashed lines indicate hydrogen interactions. Full article ">Scheme 1
Synthesis of the Schiff bases L1–L6 (L1: R2 = CF3, R1 = R3 = R4 = H; L2: R4 = CF3, R1 = R2 = R3 = H; L3: R2 = F, R1 = R3 = R4 = H; L4: R1 = F, R4 = OH, R2 = R3 = H; L5: R3 = F, R4 = OH, R1 = R2 = H; L6: R1 = R2 = R3 = R4 = H). Full article ">

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Open AccessArticle

DeBouganin Diabody Fusion Protein Overcomes Drug Resistance to ADCs Comprised of Anti-Microtubule Agents

by Shilpa Chooniedass, Rachelle L. Dillon, Arjune Premsukh, Peter J. Hudson, Gregory P. Adams, Glen C. MacDonald and Jeannick Cizeau

Molecules 2016, 21(12), 1741; https://doi.org/10.3390/molecules21121741 - 17 Dec 2016

Cited by 6 | Viewed by 5613

Abstract

Antibody drug conjugates (ADC), comprised of highly potent small molecule payloads chemically conjugated to a full-length antibody, represent a growing class of therapeutic agents. The targeting of cytotoxic payloads via the specificity and selectivity of the antibody has led to substantial clinical benefits. [...] Read more.

Antibody drug conjugates (ADC), comprised of highly potent small molecule payloads chemically conjugated to a full-length antibody, represent a growing class of therapeutic agents. The targeting of cytotoxic payloads via the specificity and selectivity of the antibody has led to substantial clinical benefits. However, ADC potency can be altered by mechanisms of resistance such as overexpression of efflux pumps or anti-apoptotic proteins. DeBouganin is a de-immunized variant of bouganin, a ribosome-inactivating protein (RIP) that blocks protein synthesis, thereby leading to apoptosis. When conjugated to trastuzumab (T-deB), deBouganin was more potent than ado-trastuzumab-emtansine (T-DM1) and unaffected by resistance mechanisms to which DM1 is susceptible. To further highlight the differentiating mechanism of action of deBouganin, HCC1419 and BT-474 tumor cells that survived T-DM1 or trastuzumab-MMAE (T-MMAE) treatment were treated with an anti-HER2 C6.5 diabody–deBouganin fusion protein or T-deB. C6.5 diabody–deBouganin and T-deB were potent against HCC1419 and BT-474 cells that were resistant to T-DM1 or T-MMAE killing. The resistant phenotype involved MDR pumps, Bcl-2 family members, and the presence of additional unknown pathways. Overall, the data suggest that deBouganin is effective against tumor cell resistance mechanisms selected in response to ADCs composed of anti-microtubule payloads. Full article

(This article belongs to the Special Issue Ribosome-Inactivating Proteins--Commemorative Issue in Honor of Professor Fiorenzo Stirpe)

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Figure 1
(A) Western Blot analysis of induced E. coli supernatants containing deB-C6.5-diab (lanes 1 and 2), C6.5-diab-deB (lanes 3 and 4), and C6.5-diab (lane 5) immunoblotted with an anti-His antibody; (B) Western Blot and Coomassie staining of purified deB-C6.5-diab (lanes 1 and 4), C6.5-diab-deB (lanes 2 and 5), and C6.5-diab (lanes 3 and 6). Purified samples resolved on an SDS-PAGE gel were either transferred to a nitrocellulose membrane and immunoblotted with an anti-His antibody (lanes 1, 2, and 3) or stained with Coomassie blue (lanes 4, 5, and 6); (C) SE-HPLC profile of purified deB-C6.5-diab with the retention time (6.745 min) indicated by the arrow; (D) Binding reactivity of C6.5-diab (dashed blue) and deB-C6.5-diab (black) against SK-BR-3 cells. Binding reactivity was determined by flow cytometry, as described in the Materials and Methods section; (E) Cytotoxicity of deB-C6.5-diab (dashed blue) and C6.5-diab-deB (black) against HER2-positive SK-BR-3 cells; (F) Kinetics of in vitro digestion of deB-C6.5-diab and C6.5-diab-deB by furin. Purified samples were incubated with recombinant furin enzyme for the indicated hours. Samples were then separated on an SDS-PAGE gel and stained with Coomassie Blue. Full article ">Figure 2
(A) Cytotoxicity of deB-C6.5-diab (blue) and deB (black) against a panel of HER2 3+ cell lines. Cytotoxicity of deB-C6.5-diab (blue), T-DM1 (red), T-MMAE (green); and T-deB (purple) against SK-BR-3 (B); BT-474 (C); and HCC1419 (D) cells. Full article ">Figure 3
Growth profiles of SK-BR-3 (A); HCC1419 (B); or BT-474 (C) cells surviving deB-C6.5-diab (blue), T-DM1 (red), T-MMAE (green) treatments, or untreated cells (black). Untreated cells or cells surviving deB-C6.5-diab, T-DM1, and T-MMAE treatments were harvested and recultured without drugs. Cell growth was measured as O.D.490 using the Cell Titer 96 Aqueous One solution cell proliferation assay at three, five, eight, and 10 days, as described in the Materials and Methods section. Full article ">Figure 3 Cont.
Growth profiles of SK-BR-3 (A); HCC1419 (B); or BT-474 (C) cells surviving deB-C6.5-diab (blue), T-DM1 (red), T-MMAE (green) treatments, or untreated cells (black). Untreated cells or cells surviving deB-C6.5-diab, T-DM1, and T-MMAE treatments were harvested and recultured without drugs. Cell growth was measured as O.D.490 using the Cell Titer 96 Aqueous One solution cell proliferation assay at three, five, eight, and 10 days, as described in the Materials and Methods section. Full article ">Figure 4
Cytotoxicity of deB-C6.5-diab (blue), T-DM1 (red), T-MMAE (green), and T-deB (purple) against HCC1419 cells surviving T-DM1 (A) or T-MMAE (B) treatments. Representative examples of two independent experiments. Full article ">Figure 5
(A) Representative images of tumorospheres from untreated (NT) HCC1419 cells or cells treated with 10 nM deB-C6.5-diab, T-DM1, or T-MMAE. (B) Representative images of tumorospheres from HCC1419 cells surviving T-DM1 or T-MMAE treatment incubated under tumorosphere-forming conditions in the presence of 10 nM deB-C6.5-diab, T-DM1, or T-MMAE. Full article ">Figure 6
(A) Western blot analysis of the expression of Bcl-xL and Mcl-1 in untreated (NT) HCC1419 cells or cells surviving T-DM1 or T-MMAE treatment. β-actin levels were monitored to ensure equal loading; (B) Cytotoxicity of T-DM1 (red) or T-MMAE (green) in the presence (dashed lines) or absence (solid lines) of ABT-737 against HCC1419 cells that survived T-DM1 (red) or T-MMAE (green) treatment. Full article ">Figure 7
Role of BCRP in BT-474 cells that survived T-DM1 or T-MMAE treatments. (A) Cytotoxicity of T-DM1 and DM1 was measured against BT-474 cells (grey bars) and T-DM1 surviving BT-474 cells with (hashed bars) or without (black bars) 10 µM Ko143; (B) Cytotoxicity of T-MMAE and MMAE was measured against BT-474 (grey bars) and T-MMAE surviving BT-474 cells with (hashed bars) or without (black bars) 10 µM Ko143. * indicates significant difference (p < 0.05). Full article ">

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Open AccessArticle

Photochemically Immobilized 4-Methylbenzoyl Cellulose as a Powerful Chiral Stationary Phase for Enantioselective Chromatography

by Eric Francotte, Dan Huynh and Tong Zhang

Molecules 2016, 21(12), 1740; https://doi.org/10.3390/molecules21121740 - 17 Dec 2016

Cited by 14 | Viewed by 4820

Abstract

A process to immobilize para-methylbenzoyl cellulose (PMBC) on silica gel has been developed and applied to prepare chiral stationary phases (CSPs) for enantioselective chromatography. The immobilization was achieved by simple irradiation of the polysaccharide derivative with ultraviolet light after coating on a [...] Read more.

A process to immobilize para-methylbenzoyl cellulose (PMBC) on silica gel has been developed and applied to prepare chiral stationary phases (CSPs) for enantioselective chromatography. The immobilization was achieved by simple irradiation of the polysaccharide derivative with ultraviolet light after coating on a silica gel support. The influence of parameters such as irradiation time and solvent on immobilization effectiveness were investigated. The performance of the prepared immobilized phases were evaluated by injection of a series of racemic compounds onto the packed columns and determination of their chiral recognition ability. By contrast to the classical coated phase, the immobilized CSP can be used under various chromatographic conditions without limitation of organic solvent types as the mobile phase. This extended applicability permits to improve selectivity and to resolve chiral compounds which are not or only poorly soluble in the mobile phases which are compatible with the non-immobilized PMBC stationary phase. Full article

(This article belongs to the Special Issue Chromatographic Separation of Enantiomers: Commemorative Issue in Honor of Professor Stig Allenmark on the Occasion of His 80th Birthday)

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Schematic photochemical setup for immobilization of PMBC on silica gel. Full article ">Figure 2
Structures of the tested racemic compounds. Full article ">Figure 3
Chromatographic resolution of compound 16. (a) on PMBC-S, mobile phase hexane/2-propanol 90/10 (v/v); (b) on PMBC-Im E, mobile phase hexane/2-propanol 90/10 (v/v); (c) on PMBC-Im E, mobile phase heptane/chloroform 75/25 (v/v). Full article ">Figure 4
Chromatographic resolution of compound 1–19 on PMBC-Im E with heptane/chloroform as the mobile phase. Enantioselectivity vs. chloroform content in heptane. Full article ">Figure 5
Chromatographic resolution of compounds 1–19 on PMBC-Im E with heptane/chloroform as the mobile phase. Retention factor k2 vs. chloroform content in heptane. Full article ">Figure 6
Chromatographic resolution of compound 19 on PMBC-Im E using heptane /chloroform mixtures as a mobile phase: (a) <img alt="Molecules 21 01740 i001" src="/molecules/molecules-21-01740/article_deploy/html/images/molecules-21-01740-i001.png"/> 60/40 (v/v); (b) ----- 75/25 (v/v); and (c) …… 90/10 (v/v). Full article ">Figure 7
Chromatographic resolution of compound 6 on PMBC-Im E using heptane /chloroform mixtures as a mobile phase: (a) <img alt="Molecules 21 01740 i001" src="/molecules/molecules-21-01740/article_deploy/html/images/molecules-21-01740-i001.png"/> 60/40 (v/v); (b) ----- 67.5/32.5 (v/v); and (c) …… 75/25 (v/v). Full article ">

1067 KiB

Open AccessArticle

Volatile and Nonvolatile Constituents and Antioxidant Capacity of Oleoresins in Three Taiwan Citrus Varieties as Determined by Supercritical Fluid Extraction

by Min-Hung Chen and Tzou-Chi Huang

Molecules 2016, 21(12), 1735; https://doi.org/10.3390/molecules21121735 - 17 Dec 2016

Cited by 33 | Viewed by 6595

Abstract

As local varieties of citrus fruit in Taiwan, Ponkan (Citrus reticulata Blanco), Tankan (C. tankan Hayata), and Murcott (C. reticulate × C. sinensis) face substantial competition on the market. In this study, we used carbon dioxide supercritical technology to [...] Read more.

As local varieties of citrus fruit in Taiwan, Ponkan (Citrus reticulata Blanco), Tankan (C. tankan Hayata), and Murcott (C. reticulate × C. sinensis) face substantial competition on the market. In this study, we used carbon dioxide supercritical technology to extract oleoresin from the peels of the three citrus varieties, adding alcohol as a solvent assistant to enhance the extraction rate. The supercritical fluid extraction was fractionated with lower terpene compounds in order to improve the oxygenated amounts of the volatile resins. The contents of oleoresin from the three varieties of citrus peels were then analyzed with GC/MS in order to identify 33 volatile compounds. In addition, the analysis results indicated that the non-volatile oleoresin extracted from the samples contains polymethoxyflavones (86.2~259.5 mg/g), limonoids (111.7~406.2 mg/g), and phytosterols (686.1~1316.4 μg/g). The DPPH (1,1-Diphenyl-2-picrylhydrazyl), ABTS [2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] scavenging and inhibition of lipid oxidation, which test the oleoresin from the three kinds of citrus, exhibited significant antioxidant capacity. The component polymethoxyflavones contributed the greatest share of the overall antioxidant capacity, while the limonoid and phytosterol components effectively coordinated with its effects. Full article

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5004 KiB

Open AccessReview

Molecular Mechanisms and Metabolomics of Natural Polyphenols Interfering with Breast Cancer Metastasis

by Yingqian Ci, Jinping Qiao and Mei Han

Molecules 2016, 21(12), 1634; https://doi.org/10.3390/molecules21121634 - 17 Dec 2016

Cited by 48 | Viewed by 10755

Abstract

Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options [...] Read more.

Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options for treating metastases. Several in vitro and in vivo studies have indicated that consumption of natural polyphenols significantly reduces the risk of cancer metastasis. Therefore, this review summarizes the research findings involving the molecular mechanisms and metabolomics of natural polyphenols and how they may be blocking breast cancer metastasis. Most natural polyphenols are thought to impair breast cancer metastasis through downregulation of MMPs expression, interference with the VEGF signaling pathway, modulation of EMT regulator, inhibition of NF-κB and mTOR expression, and other related mechanisms. Intake of natural polyphenols has been shown to impact endogenous metabolites and complex biological metabolic pathways in vivo. Breast cancer metastasis is a complicated process in which each step is modulated by a complex network of signaling pathways. We hope that by detailing the reported interactions between breast cancer metastasis and natural polyphenols, more attention will be directed to these promising candidates as effective adjunct therapies against metastatic breast cancer in the clinic. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

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Structures of the major catechins and natural polyphenols. Full article ">Figure 2
(a) Five-year Relative Survival Rates* (%) by Stage at Diagnosis, US, 2004–2010. Local: an invasive malignant tumor confined to primary organ. Regional: a malignant tumor that has extended into surrounding organs or tissues and regional lymph nodes. Distant: a malignant tumor that has spread to parts of the body remote from the primary cancer, or via the lymphatic system to distant lymph nodes; (b) The difference in relative survival rates between Regional and Distant metastases, and Value (%) = Regional–Distant. Rates* are adjusted for normal life expectancy and are based on cases diagnosed in the SEER 18 areas from 2004 to 2010, all followed through 2011, and the data are from the American Cancer Society, Inc., Surveillance Research, 2015. Full article ">Figure 3
Simplified summarizes of metastatic cascade of breast cancer and genes involving in the process of metastasis. Cancer-driven events in the metastatic cascade are delineated in time and space in a counter-clockwise beginning with the primary cancer, and then intravasation into the blood circulation, active or passive migration toward the target organ, embedding into a capillary bed, attachment to the endothelium, and extravasation, which leads to infiltration into the underlying tissue, and expansion in the target microenvironment. MMPs, matrix metalloproteinases; ZEB1, zinc finger E-box-binding homeobox 1; SLUG, zinc finger protein SNAI2; MTA3, metastasis-associated protein; MUC1: mucin 1, cell surface-associated; PSA, prostate-specific antigen; EMMPRIN: extracellular matrix metalloproteinase inducer; uPA: urokinase plasminogen activator; uPAR: urokinase plasminogen activator receptor; PAI: plasminogen activator inhibitor; RECK: reversion-inducing cysteine-rich protein with kazal motifs; PN-II: protease nexin-II; alpha1-AT: alpha 1-antitrypsin; EPCAM, epithelial cell adhesion molecule; CK19, Cytokeratin 19; CEA, carcinoembryonic antigen; SAA, serum amyloid A; LOX, protein-lysine 6-oxidase; RAC1, Ras-related C3 botulinum toxin substrate1; cdc42, cell division control protein 42 homolog; ST6GALNAC5, AGPTL4: promoting seeding; promoting colonization: OPN, CXCR4; COX-, CXCL12/CXCR4: proinflammatory molecules and chemokines/receptors; VCAM-1, TNC, OPN: adhesion and extracellular matrix molecules; SRC, NF-κB: intracellular signaling proteins. The data adapted from the study of Bos and Zhou [<a href="#B8-molecules-21-01634" class="html-bibr">8</a>,<a href="#B14-molecules-21-01634" class="html-bibr">14</a>]. Full article ">Figure 4
Model for the molecular metchanisms of natural polyphenols effects on metastasis. (A) General schematic representation of signalling pathway that regulate MMP-2 and MMP-9 expression, VEGF gene and NF-κB; (B) The proteins that promote cell-cell contact and mesenchymal markers during EMT. Full article ">

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Open AccessArticle

Safe Synthesis of Alkylhydroxy and Alkylamino Nitramines

by Simen Antonsen, Marius Aursnes, Harrison Gallantree-Smith, Christian Dye and Yngve Stenstrøm

Molecules 2016, 21(12), 1738; https://doi.org/10.3390/molecules21121738 - 16 Dec 2016

Cited by 8 | Viewed by 6039

Abstract

Three different protocols for the syntheses of hydroxyalkylnitramines are presented and compared. Safety issues regarding the synthesis of nitramines are also discussed. Full article

(This article belongs to the Section Green Chemistry)

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3139 KiB

Open AccessArticle

Synthesis and Structural Investigation of New Bio-Relevant Complexes of Lanthanides with 5-Hydroxyflavone: DNA Binding and Protein Interaction Studies

by Alexandra-Cristina Munteanu, Mihaela Badea, Rodica Olar, Luigi Silvestro, Constanţa Dulea, Constantin-Daniel Negut and Valentina Uivarosi

Molecules 2016, 21(12), 1737; https://doi.org/10.3390/molecules21121737 - 16 Dec 2016

Cited by 21 | Viewed by 6652

Abstract

In the present work, we attempted to develop new metal coordination complexes of the natural flavonoid 5-hydroxyflavone with Sm(III), Eu(III), Gd(III), Tb(III). The resultant hydroxo complexes have been characterized by a variety of spectroscopic techniques, including fluorescence, FT-IR, UV-Vis, EPR and mass spectral [...] Read more.

In the present work, we attempted to develop new metal coordination complexes of the natural flavonoid 5-hydroxyflavone with Sm(III), Eu(III), Gd(III), Tb(III). The resultant hydroxo complexes have been characterized by a variety of spectroscopic techniques, including fluorescence, FT-IR, UV-Vis, EPR and mass spectral studies. The general chemical formula of the complexes is [Ln(C₁₅H₉O₃)₃(OH)₂(H₂O)_x]·nH₂O, where Ln is the lanthanide cation and x = 0 for Sm(III), x = 1 for Eu(III), Gd(III), Tb(III) and n = 0 for Sm(III), Gd(III), Tb(III), n = 1 for Eu(III), respectively. The proposed structures of the complexes were optimized by DFT calculations. Theoretical calculations and experimental determinations sustain the proposed structures of the hydroxo complexes, with two molecules of 5-hydroxyflavone acting as monoanionic bidentate chelate ligands. The interaction of the complexes with calf thymus DNA has been explored by fluorescence titration and UV-Vis absorption binding studies, and revealed that the synthesized complexes interact with DNA with binding constants (K_b) ~ 10⁴. Human serum albumin (HSA) and transferrin (Tf) binding studies have also been performed by fluorescence titration techniques (fluorescence quenching studies, synchronous fluorescence spectra). The apparent association constants (K_a) and thermodynamic parameters have been calculated from the fluorescence quenching experiment at 299 K, 308 K, and 318 K. The quenching curves indicate that the complexes bind to HSA with smaller affinity than the ligand, but to Tf with higher binding affinities than the ligand. Full article

(This article belongs to the Section Organometallic Chemistry)

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169 KiB

Open AccessEditorial

Special Issue: “Molecules against Alzheimer”

by Michael Decker and Diego Muñoz-Torrero

Molecules 2016, 21(12), 1736; https://doi.org/10.3390/molecules21121736 - 16 Dec 2016

Cited by 3 | Viewed by 6384

Abstract

This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder [...] Read more.

This Special Issue, entitled “Molecules against Alzheimer”, gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor. The development of novel AD diagnostic agents based on tau protein imaging and the use of lithium or intranasal insulin for the prevention or the symptomatic treatment of AD is also covered in some articles of the Special Issue. Full article

(This article belongs to the Special Issue Molecules against Alzheimer)

222 KiB

Open AccessReview

The Health Benefiting Mechanisms of Virgin Olive Oil Phenolic Compounds

by Lisa Parkinson and Sara Cicerale

Molecules 2016, 21(12), 1734; https://doi.org/10.3390/molecules21121734 - 16 Dec 2016

Cited by 151 | Viewed by 14332

Abstract

Virgin olive oil (VOO) is credited as being one of the many healthful components associated with the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday Mediterranean dietary pattern. VOO [...] Read more.

Virgin olive oil (VOO) is credited as being one of the many healthful components associated with the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday Mediterranean dietary pattern. VOO is rich in phenolic compounds and the health promoting benefits of these phenolics are now established. Recent studies have highlighted the biological properties of VOO phenolic compounds elucidating their anti-inflammatory activities. This paper will review current knowledge on the anti-inflammatory and nutrigenomic, chemoprotective and anti-atherosclerotic activities of VOO phenolics. In addition the concentration, metabolism and bioavailability of specific phenolic compounds will be discussed. The evidence presented in the review concludes that oleurepein, hydroxytyrosol and oleocanthal have potent pharmacological activities in vitro and in vivo; however, intervention studies with biologically relevant concentrations of these phenolic compounds are required. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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Open AccessArticle

Validation and Application of an Ultra High-Performance Liquid Chromatography Tandem Mass Spectrometry Method for Yuanhuacine Determination in Rat Plasma after Pulmonary Administration: Pharmacokinetic Evaluation of a New Drug Delivery System

by Man Li, Xiao Liu, Hao Cai, Zhichun Shen, Liu Xu, Weidong Li, Li Wu, Jinao Duan and Zhipeng Chen

Molecules 2016, 21(12), 1733; https://doi.org/10.3390/molecules21121733 - 16 Dec 2016

Cited by 3 | Viewed by 4508

Abstract

Yuanhuacine was found to have significant inhibitory activity against A-549 human lung cancer cells. However, there would be serious adverse toxicity effects after systemic administration of yuanhuacine, such as by oral and intravenous ways. In order to achieve better curative effect and to [...] Read more.

Yuanhuacine was found to have significant inhibitory activity against A-549 human lung cancer cells. However, there would be serious adverse toxicity effects after systemic administration of yuanhuacine, such as by oral and intravenous ways. In order to achieve better curative effect and to alleviate the adverse toxicity effects, we tried to deliver yuanhuacine directly into the lungs. Ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) was used to detect the analyte and IS. After extraction (ether:dichloromethane = 8:1), the analyte and IS were separated on a Waters BEH-C₁₈ column (100 mm × 2.1 mm, 1.7 μm) under a 5 min gradient elution using a mixture of acetonitrile and 0.1% formic acid aqueous solution as mobile phase at a flow rate of 0.3 mL/min. ESI positive mode was chosen for detection. The method was fully validated for its selectivity, accuracy, precision, stability, matrix effect, and extraction recovery. This new method for yuanhuacine concentration determination in rat plasma was reliable and could be applied for its preclinical and clinical monitoring purpose. Full article

(This article belongs to the Section Medicinal Chemistry)

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Molecules, Volume 21, Issue 12 (December 2016) – 153 articles

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