- Acta Medica Nicomedia
- Vol: 6 Issue: 1
- Electronic and topological investigation of antitubercular tryptanthrin analogues and their interact...
Electronic and topological investigation of antitubercular tryptanthrin analogues and their interaction with the enoyl-ACP reductase
Authors : Fatma Aksakal Dağdelen
Pages : 82-91
Doi:10.53446/actamednicomedia.1246035
View : 14 | Download : 10
Publication Date : 2023-02-28
Article Type : Research
Abstract :Objective: This study aimed to investigate the structure-antitubercular activity relationships of a series of tryptanthrin analogues and the binding mechanisms of these analogues with InhA, Mycobacterium tuberculosis enoyl-acyl carrier protein (enoyl-ACP) reductase. Methods: Structure-activity relationships were investigated by using Electronic-Topological Method combined with Neural Networks (ETM-NN). Binding energies and non-covalent interactions stabilizing the ligand-InhA complex were obtained from the results of molecular docking. To assess these interactions, frontier molecular orbital analysis of the ligand-InhA complexes were also analysed. Results: The results of the ETM-NN application to the series of compounds in view are pharmacophoric and anti-pharmacophoric molecular fragments, which are characteristic of the class of compounds demonstrating activity against Mycobacterium tuberculosis strain H37Rv. The statistical characteristics of five pharmacophores (Phi) and five anti-pharmacophores (APhi) entering the forecasting system, are 0.90 and 0.86, correspondingly. Analysis of the electron density distribution has shown that the more effective binding with receptor was observed for active compounds. Conclusions: A system of prognosis for the anti-tubercular activity of Mycobacterium tuberculosis H37Rv was developed on the base of the pharmacophores found, docking results, and electronic structure calculations. This prognosis system allows for designing of new potent antitubercular drugs. Keywords: Tryptanthrin analogues, mycobacterium tuberculosis H37Rv, InhA electronic-topological method, molecular docking, density functional theoryKeywords : Triptantrin analogları, Mycobacterium tuberculosis H37Rv, InhA, Elektronik-topolojik yöntem, Moleküler kenetlenme, Tryptanthrin analogues