Affiliations 

  • 1 Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
  • 2 School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia
  • 3 Department of Electronics and Computer Engineering, Amrita Vishwa Vidyapeetham, Kollam, Kerala, India
  • 4 Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf university, Sakaka, Saudi Arabia
  • 5 Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
  • 6 Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, Italy
J Biomol Struct Dyn, 2023 Dec 08.
PMID: 38064315 DOI: 10.1080/07391102.2023.2291549

Abstract

Tuberculosis is one of the most ancient infectious diseases known to mankind predating upper Paleolithic era. In the current scenario, treatment of drug resistance tuberculosis is the major challenge as the treatment options are limited, less efficient and more toxic. In our study we have developed an atom based 3D QSAR model, statistically validated sound with R2 > 0.90 and Q2 > 0.72 using reported direct inhibitors of InhA (2018-2022), validated by enzyme inhibition assay. The model was used to screen a library of 3958 molecules taken from Binding DB and candidates molecules with promising predicted activity value (pIC50) > 5) were selected for further analyzed screening by using molecular docking, ADME profiling and molecular dynamic simulations. The lead molecule, ZINC11536150 exhibited good docking score (glideXP = -11.634 kcal/mol) compared to standard triclosan (glideXP =  -7.129 kcal/mol kcal/mol) and through molecular dynamics study it was observed that the 2nv6-complex of ZINC11536150 with Mycobacterium tuberculosis InhA (PDB entry: 2NV6) complex remained stable throughout the entire simulation time of 100 ns.Communicated by Ramaswamy H. Sarma.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.