3‐Aryl‐substituted imidazo[1,2‐a]pyridines as antituberculosis agents

Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3‐aryl‐substituted imidazo[1,2‐a]pyridines as potent antituberculosis agents. A small library of 3‐aryl‐substituted imidazo[1,2‐a]pyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd‐cat...

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Published in:Archiv der Pharmazie (Weinheim) 2021-10, Vol.354 (10), p.e2000419-n/a
Main Authors: Karale, Uttam B., Shinde, Akash U., Babar, Dattatraya A., Sangu, Komal G., Vagolu, Siva Krishna, Eruva, Vamshi K., Jadav, Surender S., Misra, Sunil, Dharmarajan, Sriram, Rode, Haridas B.
Format: Article
Language:English
Subjects:
3‐aryl‐substituted
Antitubercular Agents - chemical synthesis
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
antituberculosis agents
imidazo[1,2‐a]pyridine
Microbial Sensitivity Tests
Molecular Docking Simulation
Mycobacterium tuberculosis - drug effects
Pyridines - chemical synthesis
Pyridines - chemistry
Pyridines - pharmacology
Structure-Activity Relationship
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Summary:Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3‐aryl‐substituted imidazo[1,2‐a]pyridines as potent antituberculosis agents. A small library of 3‐aryl‐substituted imidazo[1,2‐a]pyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd‐catalyzed C−N coupling reactions. The compounds thus obtained were evaluated against Mycobacterium tuberculosis H37Rv. Compound 26 was identified as an antituberculosis lead with a minimum inhibitory concentration of 2.3 μg/ml against M. tuberculosis H37Rv. This compound showed a selectivity index of 35. The docking of 26 in the active site of the M. tuberculosis cytochrome bc1 complex cytochrome b subunit (Mtb QcrB) revealed key π–π interactions of compound 26 with the Tyr389 and Trp312 residues of Mtb QcrB. A small library of 3‐aryl‐substituted imidazo[1,2‐a]pyridines was synthesized using direct arylation, followed by nitro reduction and Pd‐catalyzed C–N coupling reactions. The obtained compounds were evaluated against Mycobacterium tuberculosis H37Rv, identifying compound 26 as an antituberculosis lead with a minimum inhibitory concentration of 2.3 μg/ml against M. tuberculosis H37Rv and a selectivity index of 35.
ISSN:0365-6233
1521-4184
DOI:10.1002/ardp.202000419