MOLECULAR DOCKING STUDIES OF ISATIN-LINKED CHALCONE DERIVATIVES AS ANTI-TB DRUG CANDIDATES AND THEIR ADMET PREDICTION

MARAPATLA SHINY; GIRIJA SASTRY VEDULA; KINTHADA HIMA BINDU; KALIBOGA SAI TEJA; DEVASANI JAGADEESWARA REDDY

doi:10.22159/ajpcr.2025v18i4.54015

Authors

MARAPATLA SHINY Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India
GIRIJA SASTRY VEDULA Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India
KINTHADA HIMA BINDU Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India
KALIBOGA SAI TEJA Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India
DEVASANI JAGADEESWARA REDDY Department of Pharmaceutical Biotechnology, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India

DOI:

https://doi.org/10.22159/ajpcr.2025v18i4.54015

Keywords:

Isatin-linked chalcones, Molecular docking,, InhA inhibitors, Anti-tuberculosis agents, Drug resistance, Absorption, distribution, metabolism, excretion, toxicity prediction, Structure-activity relationship

Abstract

Objective: Molecular docking studies were carried out on fifteen novel Isatin-linked chalcone derivatives to evaluate their potential as anti-tuberculosis drug candidates targeting NADH-Dependent 2-trans Enoyl–Acyl Carrier Protein Reductase (InhA).

Methods: The compounds were designed in-silico and optimized using Molegro Virtual Docker (MVD) and AutoDock tools to target the InhA enzyme (PDB ID: 4QXM). Molecular docking simulations indicated that compounds 6-9 exhibited superior binding affinities (-10.5 kcal/mol) compared to the standard drugs Isoniazid (-6.1 kcal/mol) and NAD+ (-10.3 kcal/mol).

Results: Analysis of protein-ligand interactions demonstrated that the most active compounds formed stable hydrogen bonds with key residues PHE-41, THR-39, and LEU-63 in the InhA binding pocket. ADMET predictions indicated favorable drug-like properties for all synthesized compounds, with acceptable molecular weights (350-450 Da), optimal lipophilicity (LogP< 5), and high gastrointestinal absorption rates. The compounds showed compliance with Lipinski’s rule of five and exhibited blood-brain barrier permeability.

Conclusion: The direct targeting of InhA by these chalcone derivatives, independent of KatG activation, indicates potential effectiveness against drug-resistant Mycobacterium tuberculosis strains.

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