New Imidazole Inhibitors of Mycobacterial FtsZ: the Way from High-Throughput Molecular Screening in Grid up to in vitro Verification

TitleNew Imidazole Inhibitors of Mycobacterial FtsZ: the Way from High-Throughput Molecular Screening in Grid up to in vitro Verification
Publication TypeJournal Article
Year of Publication2016
AuthorsKarpov, PA, Demchuk, OM, Britsun, VM, Lytvyn, DI, Pydiura, MO, Rayevsky, OV, Samofalova, DO, Spivak, SI, Volochnyuk, DM, Yemets, AI, Blume, Ya.B
Short TitleNauka innov.
DOI10.15407/scin12.03.044
Volume12
Issue3
SectionScientific Framework of the Innovation Activity
Pagination44-59
LanguageUkrainian
Abstract
In the framework of UNG virtual organization CSLabGrid, high-throughput molecular screening was performed for new anti-TB compounds. Using program FlexX installed on IFBG Claster and models of four perspective ligand binding sites on the surface of FtsZ of Mycobacterium tuberculosis, virtual screening was performed for database containing 2886 compounds synthesized in the Institute of Organic Chemistry of NAS of Ukraine. Based on LE and ΔG score, docking scores of CCDC Gold, and results of molecular dynamics, we selected a group of perspective FtsZ inhibitors. In vitro validation have revealed 6 compounds with the highest inhibition of GTPase activity of FtsZ. Also, based on in vitro experiment, we have selected three compounds exhibiting both - strong inhibition of FtsZ polymerization and inhibition of GTPase activity.
Keywordsbioinformatics, high-throughput screening (HTS), in vitro, structural biology, tuberculosis