Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine Mannich bases

In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by 1H NMR, 13C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C23H29ClN4]+2, H2O). The in vitro antimicrobial activities of the compounds were evaluated against various bacterial and fungal strains using Agar diffusion method and Broth micro dilution method. Compounds 7e, 7f, 7r, 7t, and 7u were showed good Gram-positive antibacterial activity against S. aureus, B. flexus, C. sporogenes and S. mutans. Furthermore, in vitro antimycobacterial activity was evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) using MABA. Compounds 7r, 7t, and 7u were showed good antitubercular activity against Mtb (MIC ≥6.25 μg/mL). Among the tested compounds, 1-((4-chloro-2-(cyclohexylmethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)methyl)piperidine-3-carboxamide (7t) was showed excellent antimycobacterial activity against Mtb (MIC >25). Molecular docking of the active compounds against glutamate racemase (MurI) and Mtb glutamine synthetase were explained the structure-activity observed in vitro. [Display omitted] •A new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v) was synthesized.•In vitro antimycobacterial evaluation of 7a-v against Mtb H37Rv was carried out.•In vitro antimicrobial evaluation of 7a-v was carried out.•Compounds 7e, 7f, 7r, 7t and 7u were showed good anti-TB, antibacterial activity and lowest toxicity.•Molecular docking of the active compounds was carried out against glutamate racemase and Mtb glutamine synthetase.