11(1)15

Nauka innov. 2015, 11(1):92-100
https://doi.org/10.15407/scin11.01.092

P.A. Karpov1, V.M. Brytsun2, A.V. Rayevsky1, O.M. Demchuk1, N.O. Pydiura1, S.P. Ozheredov1, D.A. Samofalova1, S.I. Spivak1, A.I. Yemets1, V.I. Kalchenko2, Ya.B. Blume1
1 SО «Institute of Food Biotechnology and Genomics, NAS of Ukraine», Kyiv
2 Institute of Organic Chemistry, NAS of Ukraine, Kyiv

 

High-throughput Screening of New Antimitotic Compounds Based on Potential of Virtual Organization CSLabGrid

Section: Celebrating the 10th Anniversary of the Journal
Language: Ukrainian
Abstract: In the frameworks of virtual organization CSLabGrid using Grid calculations the repository of 3-D models of cytoskeletal proteins (tubulins and FtsZ-proteins) verified by stereochemistry, is described. The repository of structures of canonical antimicrotubular compounds (inhibitors of tubulin polymerization) as well as library of ligands, suitable for high-throughput screening (HTS) in Grid were created. According to the results of the library HTS 1,164 compounds that demonstrated an elevated affinity to tubulin molecules: 205 — to α-tubulin and 959 — to β-tubulin were selected. It was found that among 2,886 compounds synthesized in the Institute of Organic Chemistry of NAS of Ukraine, 6 were perspective inhibitors of α- and β-tubulin polymerization in such human pathogens as Pneumocystis carinii, Giardia intestinalis Ajellomyces capsulatus, Neosartorya fumigata and Candida albicans. Respectively, these compounds were recommended for subsequent experimental evaluation of their biological activity for use as new pharmacological agents.
Key words: Grid, virtual organization, structural bioinformatics, cytoskeleton, tubulin, benzimidazole compounds, tubulin depolymerization, antimitotic activity, molecular docking, high-throughput screening, drugs.