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Structural modification of zolpidem led to potent antimicrobial activity in imidazo[1,2-a]pyridine/pyrimidine-1,2,3-triazoles

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Abstract

Ambien (zolpidem), an imidazo[1,2-a]pyridine derivative, is a commercial drug to treat insomnia which also possesses antitubercular activity against Mycobacterium tuberculosis H37Rv. In this paper, we describe the synthesis of three diverse lead series of imidazo[1,2-a]pyridine/pyrimidine-1,2,3-triazoles (IPTs) which are designed by specific structural modifications of zolpidem. Most of the IPTs exhibited remarkable in vitro antitubercular activity with an MIC of 1.56 μg mL−1, which is two-fold higher than the MIC of zolpidem. Further, the synthesized IPTs displayed moderate inhibitory activity against several bacterial and fungal strains as well, and also showed an acceptable safety profile as verified through in vitro cytotoxicity assessment against Vero cells. In addition, the potent IPTs exhibited promising binding interactions within the active site of the InhA enzyme. An interesting correlation between the in vitro inhibitory activity and the binding mode was observed: most of the potent molecules (MIC = 1.56 μg mL−1) interact through a H-bond with the Tyr 158 residue of the target enzyme. These efforts toward the structural modification of zolpidem could be helpful for further optimization of the IPT core to develop new anti-TB drugs.

Graphical abstract: Structural modification of zolpidem led to potent antimicrobial activity in imidazo[1,2-a]pyridine/pyrimidine-1,2,3-triazoles

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Publication details

The article was received on 04 Jul 2019, accepted on 18 Sep 2019 and first published on 19 Sep 2019


Article type: Paper
DOI: 10.1039/C9NJ03462E
New J. Chem., 2019, Advance Article

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    Structural modification of zolpidem led to potent antimicrobial activity in imidazo[1,2-a]pyridine/pyrimidine-1,2,3-triazoles

    R. Reddyrajula and U. K. Dalimba, New J. Chem., 2019, Advance Article , DOI: 10.1039/C9NJ03462E

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