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 by1H 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 <0.78 μg/mL) and low cytotoxicity against the HEK-293T cell line (SI >>25). Molecular docking of the active compounds against glutamate racemase (MurI) and Mtb glutamine synthetase were explained the structure-activity observed in vitro.
Department of Chemistry, Jain University, Bangalore 560024, Karnataka, India.
Gilish
G
Jose
Department of Chemistry, Jain University, Bangalore 560024, Karnataka, India; Department of Chemistry, University B.D.T. College of Engineering (A Constituent College of Visweswaraya Technological University, Belagavi), Davangere 577004, Karnataka, India. Electronic address: suresha.kumara@gmail.com.
Tholappanavara H
TH
Suresha Kumara
Department of Chemistry, Jain University, Bangalore 560024, Karnataka, India.
Haliwana B V
HBV
Sowmya
Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad 500078, Telangana, India.
Dharmarajan
D
Sriram
Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, Karnataka, India.
Tayur N
TN
Guru Row
Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, Karnataka, India.
Amar A
AA
Hosamani
School of Basic and Applied Sciences, Dayanand Sagara University, Bangalore 560078, India.
Sunil S
SS
More
Department of Biochemistry, Jain University, Bangalore 560011, Karnataka, India.
Bhavya
B
Janardhan
Department of Chemistry, University B.D.T. College of Engineering (A Constituent College of Visweswaraya Technological University, Belagavi), Davangere 577004, Karnataka, India; Department of MCA, Visvesvaraya Institute of Advanced Technology, Chikkaballapur 562101, Karnataka, India.
B G
BG
Harish
Department of Biotechnology, Kuvempu University, Shankarghatta 577451, Karnataka, India.
Sandeep
S
Telkar
Department of Biotechnology, M.S. Ramaiah Institute of Technology, Bangalore 560054, Karnataka, India.
Yalegara Siddappa
YS
Ravikumar
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D008352:Mannich Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D008352:Mannich Bases; D011725:Pyridines; D011758:Pyrroles; C475261:pyrrolo(3,2-c)pyridine
Antimycobacterial activity; Gram-positive antibacterial activity; Molecular docking; Pyrrolopyridine Mannich bases; Tuberculosis