Combined Pharmacophore and Molecular Docking-based In silico Study of Some Pyrrolyl 1,3,4-oxadiazole benzothioate Derivatives

Purpose: The purpose of the research was to synthesise novel pyrrole derivatives as antitubercular agents. Methodology: A series of various 5-(4-(1H-pyrrol-1-yl)phenyl)-1,3,4-oxadiazol-2-yl substituted benzothioate derivatives (5a-s) were synthesized. The newly synthesized compounds were characterized on the basis of IR, NMR and Mass spectra. The newly synthesized final compounds were evaluated for their in vitro antitubercular activity. Pharmacophore hypothesis and Surflex-Docking studies were carried out to understand the structure activity relationship. Findings: Preliminary results indicated that most of the compounds demonstrated moderate to good antitubercular activity. The effect of the nature of the substituent on the phenyl group; the effect of the hydrogen bond acceptors and the effect of the oxadiazole fragment on InhA and activities against Mycobacterium tuberculosis were assessed. The software generated results was in satisfactory agreement with the evaluated biological activity. Conclusion: These results can be exploited to develop potential leads and structure based drug design of novel InhA inhibitors.