Unveiling the therapeutic potential of azopyridine derivatives for trypsin inhibition: a DFT and In-Vitro approach
subject: Anti-inflammatory; anti-trypsin; azopyridine; pharmacophore; soft molecule
description: Heterocyclic azo derivatives have emerged as promising scaffolds for drug development. This study focused on the synthesis, computational analysis, and biological evaluation of a series of azopyridine derivatives (1a, 1d, 1 g, 1 h, 1 m, 1p, and 1s) as potential trypsin inhibitors. Density Functional Theory calculations indicated that derivative 1 h exhibited the lowest HOMO-LUMO energy gap 3.167 eV and was characterised as a soft molecule, suggesting strong binding capabilities. Molecular docking studies confirmed that 1 h binds favourably to the active site of trypsin with a glide score of ?6.581 kcal/mol and binding energy of ?29.95 kcal/mol. Along with docking studies, the stability of the trypsin-1 h complex was further analyzed using molecular dynamic simulations at 200 ns. The results showed that the ligand molecule 1 h bound strongly at the active site of trypsin. In-vitro enzyme assays determined the IC50 value of the molecule as 100 M, demonstrating enhanced potency. These results indicate that AzPy derivatives, particularly 1 h, hold considerable promise as therapeutic agents for inflammatory disorders and cancer, paving the way for further exploration in drug development and targeted therapies. Further research is warranted to explore 1hs efficacy, safety, and structure-activity relationships. Highlights: DFT studies were used to classify molecules based on their softness and hardness. Molecular docking, simulation, and in-vitro studies have identified potential anti-trypsin activity of candidate molecules. Experimental and computational calculations were in close agreement. 2024 Informa UK Limited, trading as Taylor & Francis Group.
creator: John A.M.; Suresh S.C.; Baby A.; Jayaram S.; Sarojini S.; Thomas R.; Balakrishnan S.P.
source: Molecular Physics
publisher: Taylor and Francis Ltd.
date: 2024-01-01
rights: Restricted Access
relation: ISSN: 268976; CODEN: MOPHA
format: Online
language: English
type: Article
coverage: John A.M., Department of Chemistry, School of Sciences, Christ University, Bengaluru, India; Suresh S.C., Inter-University Centre for Bioscience and Department of Biotechnology & Microbiology, Kannur University, Kannur, India; Baby A., Department of Chemistry, School of Sciences, Christ University, Bengaluru, India; Jayaram S., Department of Life Sciences, School of Sciences, Christ University, Bengaluru, India; Sarojini S., Department of Life Sciences, School of Sciences, Christ University, Bengaluru, India; Thomas R., Department of Chemistry, St. Berchmans College (Autonomous), Changanassery, India; Balakrishnan S.P., Department of Chemistry, School of Sciences, Christ University, Bengaluru, India