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Targeting the cytochrome bc1 complex for drug development in M. tuberculosis: review

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Abstract

The terminal oxidases of the oxidative phosphorylation pathway play a significant role in the survival and growth of M. tuberculosis, targeting these components lead to inhibition of M. tuberculosis. Many drug candidates targeting various components of the electron transport chain in M. tuberculosis have recently been discovered. The cytochrome bc1-aa3 supercomplex is one of the most important components of the electron transport chain in M. tuberculosis, and it has emerged as the novel target for several promising candidates. There are two cryo-electron microscopy structures (PDB IDs: 6ADQ and 6HWH) of the cytochrome bc1-aa3 supercomplex that aid in the development of effective and potent inhibitors for M. tuberculosis. In recent years, a number of potential candidates targeting the QcrB subunit of the cytochrome bc1 complex have been developed. In this review, we describe the recently identified inhibitors that target the electron transport chain's terminal oxidase enzyme in M. tuberculosis, specifically the QcrB subunit of the cytochrome bc1 complex.

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Acknowledgements

The authors would like to thank NIPER Kolkata for providing the resources and support. We would like to acknowledge the Department of Pharmaceuticals and the Ministry of Chemicals and Fertilizes for providing the fellowship to Mr. Wani.

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  1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata, West Bengal, 700054, India

    Mushtaq Ahmad Wani & Devendra Kumar Dhaked

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MAW collected the literature and wrote the manuscript. DKD revised and approved the final manuscript submitted for publication.

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Wani, M.A., Dhaked, D.K. Targeting the cytochrome bc1 complex for drug development in M. tuberculosis: review. Mol Divers 26, 2949–2965 (2022). https://doi.org/10.1007/s11030-021-10335-y

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