DESIGN, SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF NOVEL ANTI-TUBERCULAR AGENTS TARGETING GLUTAMINE SYNTHETASE-1 AND CYCLOPROPANEMYCOLIC ACID SYNTHASE-2Abstract
The World Health Organization 2015 (WHO) reports indicate that there were 9.0 million new tuberculosis (TB) cases and 1.5 million tuberculosis (TB) deaths during 2015. Co-infection with the HIV fuels the global TB crisis, and successful TB treatment is further complicated and hampered by the existence of multidrug- resistant (MDR) TB and extensively drug resistant (XDR) TB. Hence there is an urgent need for newer anti tubercular agents. Heterocyclic moieties possess profound biological activities including anti inflammatory, antitumour, antitubercular activity. The Benzothiazole nucleous and the thiophene nucleous exhibit profound pharmacological activity and so series of 2-amino thiophene derivatives were designed and docked against the enzyme glutamine synthetase-1 (PDB-ID- 4ACF) which plays an important role in the metabolism of nitrogen. Similarly, a series of Schiff bases with benzothiazole scaffolds were designed and docked against cyclopropanemycolic acid synthase-2 (PDB-ID-1KPI), the enzyme specific for synthesis of cell wall of Mycobacterium tuberculosis. Based on the docking score, interactions and docking pose molecules were screened and the selected compounds were synthesized. The synthesized compounds were purified by re-crystallization and characterized by spectral analysis (FT-IR, NMR, and Mass Spectroscopy). Anti-tubercular activity was evaluated by MABA. The present study concludes that the synthesized compounds (MMF, TM, CM and MC) show promising activity at 1.6 mcg/ml, 3.12 mcg/ml and 6.25mcg/ml against Mycobacterium tuberculosis when compared to the standard drugs like Pyrazinamide and Streptomycin.
J. Suresh*, S. G. Lakshmi, K. Madhesh, B. Karunya, K. M. Noorulla and P. R. Surya
Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Affiliated to the “The Tamil Nadu Dr. M.G.R Medical University”, Chennai, Tamil Nadu, India.
18 May, 2017
30 November, 2017
29 December, 2017
01 February, 2018