In silico design, synthesis and antitubercular activity of novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones as enoyl-acyl carrier protein reductase inhibitors - Université Toulouse III - Paul Sabatier - Toulouse INP
Article Dans Une Revue Journal of Biomolecular Structure and Dynamics Année : 2024

In silico design, synthesis and antitubercular activity of novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones as enoyl-acyl carrier protein reductase inhibitors

Résumé

Mycobacteria regulate the synthesis of mycolic acid through the fatty acid synthase system type 1 (FAS I) and the fatty acid synthase system type-2 (FAS-II). Because mammalian cells exclusively utilize the FAS-I enzyme system for fatty acid production, targeting the FAS-II enzyme system could serve as a specific approach for developing selective antimycobacterial drugs. Enoyl-acyl carrier protein reductase enzyme (MtInhA), part of the FAS-II enzyme system, contains the NADH cofactor in its active site and reduces the intermediate. Molecular docking studies were performed on an in-house database (∼2200 compounds). For this study, five different crystal structures of MtInhA (PDB Code: 4TZK, 4BQP, 4D0S, 4BGE, 4BII) were used due to rotamer difference, mutation and the presence of cofactors. Molecular dynamics simulations (250 ns) were performed for the novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones derivatives selected by molecular docking studies. Twenty-three compounds selected by in silico methods were synthesized. Antitubercular activity and MtInhA enzyme inhibition studies were performed for compounds whose structures were elucidated by IR,1H-NMR,13C-NMR, HSQC, HMBC, MS and elemental analysis.
Fichier principal
Vignette du fichier
Thesis_Paper_SIDB_HUB.pdf (1.56 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04732279 , version 1 (17-10-2024)

Identifiants

Citer

Serap İpek Dingiş Birgül, Jyothi Kumari, Rasoul Tamhaev, Lionel Mourey, Christian Lherbet, et al.. In silico design, synthesis and antitubercular activity of novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones as enoyl-acyl carrier protein reductase inhibitors. Journal of Biomolecular Structure and Dynamics, In press, ⟨10.1080/07391102.2024.2319678⟩. ⟨hal-04732279⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

More