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Drug Discov Today. 2017 Mar;22(3):510-518. doi: 10.1016/j.drudis.2016.11.006. Epub 2016 Nov 14.

DNA topoisomerase I and DNA gyrase as targets for TB therapy.

Author information

1
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India; Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India.
2
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
3
Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
4
Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: tony.maxwell@jic.ac.uk.

Abstract

Tuberculosis (TB) is the deadliest bacterial disease in the world. New therapeutic agents are urgently needed to replace existing drugs for which resistance is a significant problem. DNA topoisomerases are well-validated targets for antimicrobial and anticancer chemotherapies. Although bacterial topoisomerase I has yet to be exploited as a target for clinical antibiotics, DNA gyrase has been extensively targeted, including the highly clinically successful fluoroquinolones, which have been utilized in TB therapy. Here, we review the exploitation of topoisomerases as antibacterial targets and summarize progress in developing new agents to target DNA topoisomerase I and DNA gyrase from Mycobacterium tuberculosis.

PMID:
27856347
DOI:
10.1016/j.drudis.2016.11.006
[Indexed for MEDLINE]
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