New antituberculosis drugs targeting the respiratory chain |
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| Institution: | 1. Department of Microbiology & Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand;2. Department of Chemistry, University of Otago, PO Box 56, Dunedin 9054, New Zealand;3. MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK;1. Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand;2. Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand;3. Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand;4. Small Molecule Discovery Center, University of California, San Francisco, San Francisco, CA 94143, United States;5. School of Chemical Sciences, University of Auckland, Auckland, New Zealand;1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;2. College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang 050024, China;3. Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Parmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China;4. College of Pharmacy, Southwest Minzu University, Chengdu 610041, China;1. Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, 9054, Dunedin, New Zealand;2. Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, 1042, Auckland, New Zealand;3. Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA;1. DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa;2. Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA;3. Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;4. TB Discovery Research, Infectious Disease Research Institute, Seattle, WA 98102, USA;5. Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Republic of Singapore |
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| Abstract: | With the emergence of multidrug-resistant tuberculosis and extensive drug-resistant tuberculosis strains,there is an urgent need to develop novel drugs for the treatment of tuberculosis.The respiratory chain is a promising target for the development of newantimycobacterial agents,and a growing number of compounds have been reported and some have entered clinical trials.In this review,we summarize the main features and the electron transfer process of the mycobacterial respiratory chain,and the recent progress in the search for new small molecule inhibitors to rgeting the three main potential targets in the respiratory chain of Mycrobacterium tuberculosis.Our emphasis is on the optimization strategy of QcrB inhibitors and the challenges of developing QcrB inhibitors as antituberculosis drugs due to the alternate bd-type oxidase oxidative compensation pathway are discussed. |
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| Keywords: | Respiratory chain Antituberculosis drug QcrB NADH-2 ATP synthase |
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