Molecular dynamics simulation approach of hybrid chalcone–thiazole complex derivatives for DNA gyrase B inhibition: lead generation

Abstract

Compounds bearing thiazole and chalcone groups have been reported to be excellent leads for antibacterial, antitubercular and anticancer activities. In view of this, we performed quantitative structure–activity relationship studies using QSARINS for dataset preparation and for developing validated QSAR models that can predict novel series of thiazole–chalcone hybrids and further evaluate them for bioactivities. The molecular descriptors AATS8i, AVP-1, MoRSEE17 and GATSe7 were found to be active in predicting the structure–activity relationship. Molecular docking and dynamics simulation studies of the developed leads have shown insights into structural analysis. Furthermore, computational studies using AutoDock and Desmond predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compound 178 generated through this study creates a route for the optimization and development of novel drugs against tuberculosis infections. RMSD, RMSF, RoG, H-bond and SASA analysis confirmed the stable binding of compound 178 with the 6J90 structure. In addition, MM-PBSA and MM-GBSA also confirm the docking results. We propose the designed compound 178 as the best theoretical lead, which may further be experimentally studied for selective inhibition.