Search Results (582)

In search of novel antidiabetic agents, we synthesized a new series of chalcones with benzimidazole scaffolds by an efficient ‘one-pot’ nitro reductive cyclization method and evaluated their α-glucosidase and α-amylase inhibition studies. The ‘one-pot’ nitro reductive cyclization method offered a simple route for the preparation of benzimidazoles with excellent yield and higher purity compared to the other conventional acid- or base-catalyzed cyclization methods. ¹H, ¹³C NMR, IR, and mass spectrum data were used to characterize the compounds. Single-crystal XRD data confirmed the 3D structure of compound 7c, which was crystalized in the P$\overline{1}$ space group of the triclinic crystal system. Hirshfeld surface analysis validates the presence of O-H..O, O-H…N, and C-H…O intermolecular hydrogen bonds. From the DFT calculations, the energy gap between the frontier molecular orbitals in 7c was found to be 3.791 eV. From the series, compound 7l emerged as a potent antidiabetic agent with IC₅₀ = 22.45 ± 0.36 µg/mL and 20.47 ± 0.60 µg/mL against α-glucosidase and α-amylase enzymes, respectively. The in silico molecular docking studies revealed that compound 7l has strong binding interactions with α-glucosidase and α-amylase proteins. Molecular dynamics studies also revealed the stability of compound 7l with α-glucosidase and α-amylase proteins. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, and respiratory syncytial virus (RSV) are significant global health threats. The need for low-cost, easily synthesized oral drugs for rapid deployment during outbreaks is crucial. Broad-spectrum therapeutics, or pan-antivirals, are designed to target multiple viral pathogens simultaneously by focusing on shared molecular features, such as common metal cofactors or conserved residues in viral catalytic domains. This study introduces a new generation of potent sartans, known as bisartans, engineered in our laboratories with negative charges from carboxylate or tetrazolate groups. These anionic tetrazoles interact strongly with cationic arginine residues or metal cations (e.g., Zn²⁺) within viral and host target sites, including the SARS-CoV-2 ACE2 receptor, influenza H1N1 neuraminidases, and the RSV fusion protein. Using virtual ligand docking and molecular dynamics, we investigated how bisartans and their analogs bind to these viral receptors, potentially blocking infection through a pan-antiviral mechanism. Bisartan, ACC519TT, demonstrated stable and high-affinity docking to key catalytic domains of the SARS-CoV-2 NSP3, H1N1 neuraminidase, and RSV fusion protein, outperforming FDA-approved drugs like Paxlovid and oseltamivir. It also showed strong binding to the arginine-rich furin cleavage sites S1/S2 and S2′, suggesting interference with SARS-CoV-2’s spike protein cleavage. The results highlight the potential of tetrazole-based bisartans as promising candidates for developing broad-spectrum antiviral therapies. Full article

The era of chemotherapy began in the 1940s, which is the basis of traditional antitumor approaches and, being one of the most high-tech treatment methods, is still widely used to treat various types of cancer. A promising direction in modern medicinal chemistry is currently the creation of hybrid molecules containing several pharmacophore fragments of different structures. This strategy is successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce side effects. In this work, we synthesized 10 1-aryl derivatives of benzimidazole and benzotriazole and 11 hybrids based on them. Among the compounds obtained, the most promising hybrid molecules were diphenylamines, containing an amino group and a benzotriazole cycle in the ortho position to the bridging NH group, which showed significant cytotoxic activity, excellent antioxidant properties and the ability to suppress the migration activity of tumor cells. Taken together, our results demonstrate that substituted diphenylamine-based bipharmacophoric compounds may serve as a promising platform for further optimization to obtain effective antitumor compounds. Full article

Caffeic acid phenethyl ester (CAPE) is a phenolic natural product with diverse biological activities, notably anticancer properties. However, its ester group is metabolically unstable. The amide derivative, CAPA, offers improved metabolic stability to esterases but still possesses a metabolically liable catechol group. In this work, we describe the synthesis of a novel CAPA analogue in which the catechol is replaced with a benzimidazole bioisostere via a water-mediated Wittig reaction. Full article

Dichloro-bis(1-cinnamyl-benzimidazole)-cobalt(II) was prepared in one step using a cobalt precursor CoCl₂ and corresponding substituted benzimidazole. The complex was fully characterized using IR, elemental analysis, and mass- and NMR spectroscopy. In the solid state, the cobalt atom displays a typical tetrahedral geometry and is coordinated to two chlorine atoms and two benzimidazole moieties. Full article

A number of N-heterocyclic carbene–silver compounds (NHCs)AgX were tested in the direct carboxylation of terminal alkynes using carbon dioxide as the C1 carbon feedstock. The reactions proceed at a pressure of 1 atm of CO₂ at room temperature, in the presence of Cs₂CO₃, and using silver–NHC complexes as catalysts. Thus, phenylacetylene and several alkynes are converted to the corresponding propiolic acids in good to high conversions. The activity of the catalysts is strongly influenced by the substituents on the NHC backbone and the nature of the counterion. Specifically, the most active compound exhibits iodide as the counterion and is stabilized by a benzimidazole derivative. After 24 h of reaction, a quantitative conversion is obtained utilizing DMF as the solvent and phenylacetylene as the substrate. Full article

In the aging process, skin morphology might be affected by wrinkle formation due to the loss of elasticity and resilience of connective tissues linked to the cleavage of elastin by the enzymatic activity of elastase. Little information is available about the structural requirements to efficiently inhibit elastase 1 (EC 3.4.21.36) expressed in skin keratinocytes. In this study, a structure-based approach led to the identification to the pharmacophoric hypotheses that described the main structural requirements for binding to porcine pancreatic elastase as a valuable tool for the development of skin therapeutic agents due to its similarity with human elastase 1. The obtained models were subsequently refined through the application of computational alanine-scanning mutagenesis to evaluate the effect of single residues on the binding affinity and protein stability; in turn, molecular dynamic simulations were carried out; these procedures led to a simplified model bearing few essential features, enabling a reliable collection of chemical features for their interactions with elastase. Then, a virtual screening campaign on the in-house library of synthetic compounds led to the identification of a nonpeptide-based inhibitor (IC₅₀ = 60.4 µM) belonging to the class of N-substituted-1H-benzimidazol-2-yl]thio]acetamides, which might be further exploited to obtain more efficient ligands of elastase for therapeutic applications. Full article

Drug repurposing is a strategy to discover new therapeutic uses for existing drugs, which have well-established toxicity profiles and are often more affordable. This approach has gained significant attention in recent years due to the high costs and low success rates associated with traditional drug development. Drug repositioning offers a more time- and cost-effective path for identifying new treatments. Several FDA-approved non-chemotherapy drugs have been investigated for their anticancer potential. Among these, anthelmintic benzimidazoles (such as albendazole, mebendazole, and flubendazole) have garnered interest due to their effects on microtubules and oncogenic signaling pathways. Blood cancers, which frequently develop resistance and have high mortality rates, present a critical need for effective therapies. This review highlights the recent advances in repurposing benzimidazoles for blood malignancies. These compounds induce cell cycle arrest, differentiation, tubulin depolymerization, loss of heterozygosity, proteasomal degradation, and inhibit oncogenic signaling to exert their anticancer effects. We also discuss current limitations and strategies to overcome them, emphasizing the potential of combining benzimidazoles with standard therapies for improved treatment of hematological cancers. Full article

Despite the great effort that has gone into developing new molecules as multitarget compounds to treat Alzheimer’s disease (AD), none of these have been approved to treat this disease. Therefore, it will be interesting to determine whether benzazoles such as benzimidazole, benzoxazole, and benzothiazole, employed as pharmacophores, could act as multitarget drugs. AD is a multifactorial disease in which several pharmacological targets have been identified—some are involved with amyloid beta (Aβ) production, such as beta secretase (BACE1) and beta amyloid aggregation, while others are involved with the cholinergic system as acetylcholinesterase (AChE) and butirylcholinesterase (BChE) and nicotinic and muscarinic receptors, as well as the hyperphosphorylation of microtubule-associated protein (tau). In this review, we describe the in silico and in vitro evaluation of benzazoles on three important targets in AD: AChE, BACE1, and Aβ. Benzothiazoles and benzimidazoles could be the best benzazoles to act as multitarget drugs for AD because they have been widely evaluated as AChE inhibitors, forming π–π interactions with W286, W86, Y72, and F338, as well as in the AChE gorge and catalytic site. In addition, the sulfur atom from benzothiazol interacts with S286 and the aromatic ring from W84, with these compounds having an IC₅₀ value in the μM range. Also, benzimidazoles and benzothiazoles can inhibit Aβ aggregation. However, even though benzazoles have not been widely evaluated on BACE1, benzimidazoles evaluated in vitro showed an IC₅₀ value in the nM range. Therefore, important chemical modifications could be considered to improve multitarget benzazoles’ activity, such as substitutions in the aromatic ring with electron withdrawal at position five, or a linker 3 or 4 carbons in length, which would allow for better interaction with targets. Full article

Three novel Zn(II) mononuclear complexes with the general formula ZnL₂Cl₂ (L = 2-(4-R-phenylmethylene)benzimidazol-2-hydrazines; R-H (1), R-CH₃ (2), and R-OCH₃ (3)) were synthesized and fully characterized by various means. These complexes demonstrate excitation-dependent emission, which is detected by a change in the emission color (from blue to green) upon an increase in the excitation wavelength. Moreover complex 1 shows reversible mechanochromic luminescence behavior due to the reversible loss of solvated methanol molecules upon the intense grinding of crystals. In addition, 1 exhibits vapochromic properties, which originate from the adsorption methanol vapor on the crystal surface. The strengthening of anthelmintic activity at the transition from free hydrazones to zinc-based complexes is shown. Full article

2-Chloropyridine-3-carbonitrile derivative 1 was utilized as a key precursor to build a series of linear and angular annulated pyridines linked to a 6-hydroxy-4,7-dimethoxybenzofuran moiety. Reaction of substrate 1 with various hydrazines afforded pyrazolo[3,4-b]pyridines. Treatment of substrate 1 with 1,3-N,N-binucleophiles including 3-amino-1,2,4-triazole, 5-amino-1H-tetrazole, 3-amino-6-methyl-1,2,4-triazin-5(4H)-one and 2-aminobenzimidazole produced the novel angular pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidine, pyrido[3,2-e][1,2,4]tetrazolo[1,5-a]pyrimidine, pyrido[3′,2′:5,6] pyrimido[2,1-c][1,2,4]triazine and benzo[4,5]imidazo[1,2-a]pyrido[3,2-e]pyrimidine, respectively. Reaction of substrate 1 with 1,3-C,N-binucleophiles including cyanoacetamides and 1H-benzimidazol-2-ylacetonitrile furnished 1,8-naphthyridines and benzoimidazonaphthyridine. Moreover, reacting substrate 1 with 5-aminopyrazoles gave pyrazolo[3,4-b][1,8]naphthyridines. Finally, reaction of compound 1 with 6-aminouracils as cyclic enamines yielded pyrimido[4,5-b][1,8]naphthyridines. Some of the synthesized products showed noteworthy antimicrobial efficiency against all types of microbial strains. Structures of the produced compounds were established using analytical and spectroscopic tools. Full article

The progress in polymer science and nanotechnology yields new colloidal and macromolecular objects and their combinations, which can be defined as complex polymer materials. The complexity may include a complicated composition and architecture of macromolecular chains, specific intermolecular interactions, an unusual phase behavior, and a structure of a multi-component polymer-containing material. Determination of a relation between the structure of a complex material, the structure and properties of its constituent elements, and the rheological properties of the material as a whole is the subject of structural rheology—a valuable tool for the development and study of novel materials. This work summarizes the author’s structural–rheological studies of complex polymer materials for determining the conditions and rheo-manifestations of their micro- and nanostructuring. The complicated chemical composition of macromolecular chains and its role in polymer structuring via block segregation and cooperative hydrogen bonds in melt and solutions is considered using tri- and multiblock styrene/isoprene and vinyl acetate/vinyl alcohol copolymers. Specific molecular interactions are analyzed in solutions of cellulose; its acetate butyrate; a gelatin/carrageenan combination; and different acrylonitrile, oxadiazole, and benzimidazole copolymers. A homogeneous structuring may result from a conformational transition, a mesophase formation, or a macromolecular association caused by a complex chain composition or specific inter- and supramolecular interactions, which, however, may be masked by macromolecular entanglements when determining a rheological behavior. A heterogeneous structure formation implies a microscopic phase separation upon non-solvent addition, temperature change, or intense shear up to a macroscopic decomposition. Specific polymer/particle interactions have been examined using polyethylene oxide solutions, polyisobutylene melts, and cellulose gels containing solid particles of different nature, demonstrating the competition of macromolecular entanglements, interparticle interactions, and adsorption polymer/particle bonds in governing the rheological properties. Complex chain architecture has been considered using long-chain branched polybutylene-adipate-terephthalate and polyethylene melts, cross-linked sodium hyaluronate hydrogels, asphaltene solutions, and linear/highly-branched polydimethylsiloxane blends, showing that branching raises the viscosity and elasticity and can result in limited miscibility with linear isomonomer chains. Finally, some examples of composite adhesives, membranes, and greases as structured polymeric functional materials have been presented with the demonstration of the relation between their rheological and performance properties. Full article

The synthesis and characterization of two novel diastereomeric Mannich bases was carried out from the reaction of the cyclic aminal (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo[8.8.1.1.^8,170.^2,70.^11,16]icosane 1 and p-cresol 2a and 4-methoxyphenol 2b in a water/dioxane mixture. The title compounds (4a–b) are interesting because bearing two 3-(2-hydroxy-5-substitutedbenzyl)octahydro-1H-benzimidazol-1-yl]methyl} substituents joined to an arenol ring. The formation of these new Mannich bases in the reaction mixture can be explained by aminomethylation of previously reported di-Mannich base 2,2′-((hexahydro-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(methylene))bis(4-substituentphenol) 3a–b. NMR analysis demonstrated that compounds 4a–b were formed as diastereomeric mixtures. Subsequent experiments revealed that at longer reaction times, the percentage yield of these new products increased considerably (yield percentages up to 22–27%), suggesting a nucleophilic competition between the p-substituted phenols and Mannich bases of type 3 for aminal 1. Full article

Background and Objectives: Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigating new therapeutic approaches is necessary. Materials and Methods: Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription–quantitative polymerase chain reaction technologies. Results: Tested at various concentrations, the half-maximal inhibitory concentrations (IC₅₀) of IMBZC on HT29 and SW620 cell growth were determined to be 22.13 µM (6.97 μg/mL) and 15.53 µM (4.89 μg/mL), respectively. IMBZC did not alter the cell growth of normal HEK293 cell lines. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyses revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. Conclusions: This study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC. Full article