Papers by Dmitry Osolodkin
Journal of Cheminformatics, 2011
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Molecular Informatics, 2014
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Journal of Organometallic Chemistry, 2015
ABSTRACT A series of cytotoxic organotin compounds with Sn–S bonds of formulae Me2Sn(SR)2 (1); Et... more ABSTRACT A series of cytotoxic organotin compounds with Sn–S bonds of formulae Me2Sn(SR)2 (1); Et2Sn(SR)2 (2); (n-Bu)2Sn(SR)2 (3); Ph2Sn(SR)2 (4); R2Sn(SR)2 (5); Me3SnSR (6) Ph3SnSR (7) (R = 3,5-di-tert-butyl-4-hydroxyphenyl), synthesized recently, have been used to study the possible mechanisms of their cytotoxicity. With this aim we have investigated the influence of organotin compounds 1–7 as well as their precursor R2SnCl2 (8) on tubulin assembly in microtubules. Compounds 1, 6–8 reveal the statistically significant inhibition of tubulin polymerization without notable disturbances of microtubules structure. Docking simulations revealed the possibility of organotin compounds to bind in the paclitaxel or vinblastine sites on the tubulin surface, but the mechanism of action of the compounds could not be explained based solely on these data. The influence on mitochondrial potential and induction of mitochondrial permeability transition also have been studied. Organotin compound 7 depolarises the mitochondria and induces the mitochondrial permeability transition. These properties may be the main reason of its cytotoxicity. Since the organotins possess the protective 2,6-di-tert-butylphenol groups the antioxidant potential of these compounds as inhibitors of mitochondrial lipid peroxidation was studied. All compounds under investigation effectively inhibit the Fe3+-induced mitochondrial lipid peroxidation. The comparative study of structure-activity relationship in the lipid peroxidation inhibition was performed. The influence of the organic groups nature, the number of hindered phenol fragments in organotins on their toxic effect is discussed. The introduction of hindered phenol groups decreases the cytotoxicity of compounds. This result opens up the possibility of designing novel anticancer drugs that might possess lower undesirable toxicity against normal cells.
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Journal of experimental botany, Jan 21, 2015
Cytokinin receptors play a key role in cytokinin-dependent processes regulating plant growth, dev... more Cytokinin receptors play a key role in cytokinin-dependent processes regulating plant growth, development, and adaptation; therefore, the functional properties of these receptors are of great importance. Previously the properties of cytokinin receptors were investigated in heterologous assay systems using unicellular microorganisms, mainly bacteria, expressing receptor proteins. However, within microorganisms receptors reside in an alien environment that might distort the receptor properties. Therefore, a new assay system has been developed allowing studies of individual receptors within plant membranes (i.e. closer to their natural environment). The main ligand-binding characteristics of receptors from Arabidopsis [AHK2, AHK3, and AHK4] and maize (ZmHK1) were refined in this new system, and the properties of full-length Arabidopsis receptor AHK2 were characterized for the first time. Ligand specificity profiles of receptors towards cytokinin bases were comparable with the profiles ...
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Acta naturae, 2012
Cytokinins belong to one of the most important and well-known classes of plant hormones. Discover... more Cytokinins belong to one of the most important and well-known classes of plant hormones. Discovered over half a century ago, cytokinins have retained the attention of researchers due to the variety of the effects they have on the growth and development of vegetable organisms, their participation in a plant adaptation to external conditions, and the potential to be used in biotechnology, agriculture, medicine and even cosmetics. The molecular mechanism by which cytokinins function remained unknown for a long time. Things started to change only in the 21(st)century, after the discovery of the receptors for these phytohormones. It appeared that plants found ways to adapt a two-component signal transduction system borrowed from prokaryotic organisms for cytokinin signalling. This review covers the recent advances in research of the molecular basis for the perception and transduction of the cytokinin signal. Emphasis is placed on cytokinin receptors, their domain and three-dimensional st...
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Natural product communications, 2012
Subtle balance of inter- and intramolecular hydrogen bond strength in aqueous solutions often gov... more Subtle balance of inter- and intramolecular hydrogen bond strength in aqueous solutions often governs the structure and dynamics of molecular species used as potential drugs and in supramolecular applications. In silico molecular dynamics study of water solution of manzamine A has been performed with different atomic charges in order to investigate the influence of charge distribution choice on predicting qualitative and quantitative features of the simulated systems. Various well known charge schemes (MK-ESP, RESP, Mulliken, AMI-BCC, Gasteiger-Hückel, Gasteiger-Marsili, MMFF94, and Dynamic Electronegativity Relaxation - DENR) led to qualitatively different pictures of dynamic behavior of the intramolecular hydrogen bond. The reported calculation framework represents a relatively rare case where differences in charge distributions lead to noticeable differences in simulated properties, thus providing a useful test case for force field and charge distribution development, provided hi...
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Page 1. GABAA and GABAC Receptors: Molecular Modelling and QSAR Analysis of Selective Ligands Vla... more Page 1. GABAA and GABAC Receptors: Molecular Modelling and QSAR Analysis of Selective Ligands Vladimir A. Palyulin, Vladimir I. Chupakhin, Dmitry I. Osolodkin, Eugene V. Radchenko, Nikolay S. Zefirov Department of ...
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Org. Biomol. Chem., 2015
Tick-borne encephalitis virus (TBEV) belonging to Flavivirus genus causes severe infection in hum... more Tick-borne encephalitis virus (TBEV) belonging to Flavivirus genus causes severe infection in humans. The search for therapeutically relevant compounds targeting TBEV requires the exploration of novel chemotypes. A versatile synthesis of previously unknown 4-aminopyrimidines and 4-aminopyrimidine N-oxides based on a fluorosubstituted heterocyclic core is described. A representative series of 4-aminotetrahydroquinazoline derivatives, containing aliphatic and aromatic substituents as well as the adamantane framework, was obtained and their activity against tick-borne encephalitis virus reproduction was studied. Nine compounds were found to inhibit TBEV entry into the host cells. A bulky hydrophobic adamantyl group was identified to be important for the antiviral activity. The developed synthetic route allowed an easy access to a consistent compound library for further structure-activity relationship studies.
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Virology, 2010
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Doklady Biochemistry and Biophysics, 2010
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Doklady Biochemistry and Biophysics, 2007
Without Abstract
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Russian Chemical Bulletin, 2011
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Russian Chemical Bulletin, 2010
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Proteins: Structure, Function, and Bioinformatics, 2012
Eukaryotic-like serine/threonine protein kinases (ESTPKs) are widely spread throughout the bacter... more Eukaryotic-like serine/threonine protein kinases (ESTPKs) are widely spread throughout the bacterial genomes. These enzymes can be potential targets of new antibacterial drugs useful for the treatment of socially important diseases such as tuberculosis. In this study, ESTPKs of pathogenic, probiotic, and antibiotic-producing Gram-positive bacteria were classified according to the physicochemical properties of amino acid residues in the ATP-binding site of the enzyme. Nine residues were identified that line the surface of the adenine-binding pocket, and ESTPKs were classified based on these signatures. Twenty groups were discovered, five of them containing >10 representatives. The two most abundant groups contained >150 protein kinases that belong to the various branches of the phylogenetic tree, whereas certain groups are genus- or even species-specific. Homology modeling of the typical representatives of each group revealed that the classification is reliable, and the differences between the protein kinase ATP-binding pockets predicted based on their signatures are apparent in their structure. The classification is expected to be useful for the selection of targets for new anti-infective drugs.
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PLoS ONE, 2014
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PLoS ONE, 2013
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Plant Cell Reports, 2013
Cytokinins are ubiquitous plant hormones; their signal is perceived by sensor histidine kinases-c... more Cytokinins are ubiquitous plant hormones; their signal is perceived by sensor histidine kinases-cytokinin receptors. This review focuses on recent advances on cytokinin receptor structure, in particular sensing module and adjacent domains which play an important role in hormone recognition, signal transduction and receptor subcellular localization. Principles of cytokinin binding site organization and point mutations affecting signaling are discussed. To date, more than 100 putative cytokinin receptor genes from different plant species were revealed due to the total genome sequencing. This allowed us to employ an evolutionary and bioinformatics approaches to clarify some new aspects of receptor structure and function. Non-transmembrane areas adjacent to the ligand-binding CHASE domain were characterized in detail and new conserved protein motifs were recovered. Putative mechanisms for cytokinin-triggered receptor activation were suggested.
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Parasitology, 2011
Glycogen synthase kinase 3 (GSK-3) is a promising target for the treatment of various human disea... more Glycogen synthase kinase 3 (GSK-3) is a promising target for the treatment of various human diseases such as type 2 diabetes, Alzheimer's disease and inflammation. Successful inhibition of the homologues of this kinase in Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani makes the kinase an attractive target for the treatment of malaria, trypanosomiasis and leishmaniasis, respectively. The aim of this work was to compare the binding sites of the GSK-3 kinases of different parasites and to analyse them as possible targets for therapeutic compounds. Both a sequence alignment and homology models of the structure of 21 different GSK-3 homologues belonging to mammals, insects, pathogenic fungi, nematodes, trematodes and protozoa have been analysed, 17 of them being studied for the first time. The structure of the kinases and, in particular, their binding sites, were found to be rather conserved, possessing small insertions or deletions and conserved amino acid substitutions. Nevertheless, the kinases of most species of parasite did have some amino acid differences from the human kinase, which could be exploited for the design of selective drugs. Comparison of the human and parasite GSK-3 ATP binding site models has shown that the development of selective drugs affecting parasite GSK-3 is possible. Known inhibitors of human GSK-3 can also be used as starting scaffolds for the search for drugs acting against parasitic diseases.
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Papers by Dmitry Osolodkin