摘要
由结核分枝杆菌(MTB)引起的结核病(TB)是全球死亡的主要原因之一,每年估计有150万人死亡。大多数感染病例报告来自东南亚地区,包括印度。在1943年发现链霉素和1945年发现其抗结核活性后,药物发现努力确定异烟肼、乙胺丁醇和利福平为结核活性。然而,多年来,由于分枝杆菌菌株的基因突变,这些药物已经成为无效的。这已经将药物发现的努力转移到识别耐药形式的细菌的新靶点和药物上。ATP合酶被确定为MDR-TB的关键靶点之一。本文综述为ATP合酶靶点、二芳基喹啉类抑制剂的结构活性关系研究(SAR)及其与治疗MDR-TB的临床相关性提供了关键的见解。
关键词: ATP合酶、结核病、二芳基喹啉、贝达喹碱、分枝杆菌、药物靶点。
Current Drug Targets
Title:ATP Synthase, an Emerging Target in TB Drug Discovery: Review of SAR and Clinical Pharmacology of Diarylquinoline Inhibitors
Volume: 22 Issue: 11
关键词: ATP合酶、结核病、二芳基喹啉、贝达喹碱、分枝杆菌、药物靶点。
摘要: Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is one of the leading causes of mortality worldwide, with an estimated 1.5 million deaths annually. The majority of infection cases are reported from the Southeast Asian region, including India. After the discovery of Streptomycin in 1943 and its anti-tubercular activity in 1945, drug discovery efforts identified Isoniazid, Ethambutol, and Rifampin as TB-actives. However, over the years, these drugs have been rendered ineffective due to genetic mutations in mycobacterial strains. This has shifted drug discovery efforts towards identifying new targets and drugs for drug-resistant forms of bacteria. ATP synthase was identified as one of the key targets of MDR-TB. This review provides key insights into the ATP synthase target, structure activity relationship studies (SAR) of diarylquinoline class of inhibitors and their clinical relevance for treating MDR-TB.
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ATP Synthase, an Emerging Target in TB Drug Discovery: Review of SAR and Clinical Pharmacology of Diarylquinoline Inhibitors, Current Drug Targets 2021; 22 (11) . https://dx.doi.org/10.2174/1389450122666210122084332
DOI https://dx.doi.org/10.2174/1389450122666210122084332 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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