Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
Tuberculosis (Edinb). 2019 Jul;117:79-84. doi: 10.1016/j.tube.2019.06.005. Epub 2019 Jun 24.
Bedaquiline was approved by USFDA in 2012 for pulmonary MDR-TB. The IC value of bedaquiline was reported to be remarkably low (25 nM), effectively inhibiting mycobacterial ATP synthase. In addition to these obvious assets of bedaquiline, the potential disadvantages of bedaquiline include inhibition of the hERG (human Ether-à-go-related gene; KCNH) potassium channel (concurrent risk of cardiac toxicity), hepatic toxicity and possibly phospholipidosis. The current review focuses primarily on the structural part of bedaquiline for the activity-toxicity optimization. This critical analysis of the structure of bedaquiline will help medicinal chemists to synthesize the better modified analouge of bedaquiline with reduced cardiotoxicity, hepatotoxicity potential and improved pharmacokinetics.
贝达喹啉于 2012 年被美国食品药品监督管理局批准用于治疗耐多药肺结核。贝达喹啉的 IC 值被报道为非常低（25nM），有效地抑制分枝杆菌的 ATP 合酶。除了这些明显的贝达喹啉优势外，贝达喹啉的潜在缺点还包括抑制 hERG（人类 Ether-à-go-related gene；KCNH）钾通道（同时存在心脏毒性的风险）、肝毒性和可能的磷脂沉积症。本综述主要集中在贝达喹啉的结构部分，以实现活性-毒性优化。对贝达喹啉结构的这种关键分析将帮助药物化学家合成更好的改良贝达喹啉类似物，降低心脏毒性、肝毒性的可能性，并改善药代动力学。
