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  • Chem Sci Trans., 2015, 4(1),  pp 1-16  

    DOI:10.7598/cst2015.936

    Research Article

    Design and One-Pot Synthesis of (1H, 3H) Imidazo[4,5-b] Pyridines: Novel Therapeutic Agents Against M. Tuberculosis

  • SUNIL L. HARER and MANISH S. BHATIA
  • Department of Pharmaceutical Chemistry, Bharati Vidyapeeth’s College of Pharmacy, Near Chitranagari, Kolhapur-416013, (M.S), India
  • Abstract

    Prevalence to the various biological activities of imidazo[4,5-b] pyridine nucleus has promoted us for an attempt of one pot synthesis of (1H, 3H) imidazo [4,5-b] pyridines (desazopurines) as inhibitors of Lumazine synthase in M. Tuberculosis (PDB 2C92). Major advantage of Lumazine synthase enzyme behind consideration as target protein in docking study is its absence in mammalian cell but presence in various reported microorganism. All synthesized compounds were characterized by spectral studies (FT-IR, 1H NMR, 13C NMR and HR-MS), elemental analysis (C, H and N). In docking analysis best fit in the active pocket of target protein found were 4-(3H-imidazo[4,5-b]pyridin-2-yl)-2-methoxyphenol (1f) and 4-(2-methyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-yl)benzene-1,2,3-triol (2b) studied further for binding interactions. Microplate Alamar Blue Assay (MABA) method used for in vitro anti-tubercular testing has revealed 1-(3H-imidazo[4,5-b]pyridin-2-yl)-butane-1,2,3,4-tetraol (1a), 1-(3H-imidazo[4,5-b]pyridin-2-yl)pentane-1,2,3,4,5-pentol (1b), 1-(3H-imidazo[4,5-b]pyridin-2-yl) butane-1,2,3,4-tetrol (1c), 4-(3H-imidazo[4,5-b]pyridin-2-yl)benzene-1,2-diol (1j), 4-chloro-2-(2-methyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-yl)phenol (2a), 3-(aminomethyl)-4-(2-methyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-l)benzene-1,2-diol (2c), 4-(2-methyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-yl)benzene-1,3-diol (2f) were found potentially significant anti-tubercular agents (MIC=3.12 µg/mL). These compounds could be considered as promising leads over the Pyrazinamide (MIC= 3.125 µg/mL) and Streptomycin (MIC= 6.25 µg/mL). Present study could be a unique source for development of newer therapeutic agents in the treatment of infection by M. tuberculosis.

    Keywords

    Imidazo[4,5-b]pyridine, Lumazine synthase, M. tuberculosis, MABA, Structure activity relationship

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