Abstract

DESIGN, SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF SOME NOVEL THIADIAZOLE, IMIDAZOLE AND INDOLE DERIVATIVES AS ANTITUBERCULAR AGENTS AGAINST TARGET ENZYME GLUTAMINE SYNTHETASE I

Ayyadurai Jerad Suresh*, Esakki Ayyamperumal, Murugesan Pachamuthu, Fathima Jesiya and Parakkot Ramakrishnan Surya

ABSTRACT

Tuberculosis is a chronic granulomatous disease which is a major health problem in developing countries. The Anti-tubercular drugs for the treatment of Tuberculosis are complicated by the existence of Multi Drug Resistance (MDR) tuberculosis, Extensively Drug Resistance (XDR) tuberculosis and Totally Drug Resistant (TDR) tuberculosis. In this research work, thiadiazole, imidazole and indole derivatives were designed and docked against target enzyme of Mtb Glutamine synthetase I (PDB ID: 3zxr) using Auto Dock 4® tools. The best binding score of the docked molecule were screened for drug likeness (Lipinski‟s rule) using Molinspiration® followed by toxicity by OSIRIS® property explorer. Anti-tubercular activity was evaluated against Mycobacterium tuberculosis (H37RV) by microplate alamar blue assay (MABA). In the present study, the synthesized compounds (a,b,c,d,e,f and g) show promising activity between 6.25μg/ml to 1.6μg/ml against Mycobacterium tuberculosis similar to the standard drugs like pyraziamide and streptomycin. The toxicity studies like acute toxicity and cytotoxicity were performed.

Keywords: Anti-tubercular agents, Glutamine synthetase I, Thiadiazole, Imidazole, Indole.