Designing of Novel Inhibitors of Mycobacterium Tuberculosis H37Rv by Pharmacophore based Drug Designing and its Evaluation
Faizan Ahmad, Kaushal K. Chandrul, Huma Umber Naz, Neeraj Tandan · International Journal of Current Research and Academic Review · 2016
The growing frequency of drug-resistant tuberculosis, which is resistant to valuable multiple antibiotic, presents a major global health warning. Filamenting temperature-sensitive mutant gene-Z (FtsZ) a tubulin homologue involved in bacterial cell division is considered an attractive target for the development of effective antibiotics against tuberculosis. In this study, we attempted to identify novel ZINC compounds that specifically target the M. tuberculosis H37Rv, FtsZ protein and docked on the FtsZ protein crystal Structure (PDB Id: 1RLU, resolution 2.08 Å). We have developed a pharmacophore model based on the already existing drugs and drug candidates with PHASE module of Schrodinger. This pharmacophore was used to screen against the prepared fragment-like and drug-like natural compound dataset (ZINC database) with altogether different scaffold using high throughput virtual screening and docking studies. Finally, we have reported eight top scoring compounds which possess high affinity for active site of FtsZ protein as well as showed the highest docking score and H-bond interaction and thus, can be considered as potential FtsZ inhibitors for the treatment of tuberculosis.