Curtin Medical School, Faculty of Health Sciences, Curtin University, Bentley, Perth, WA 6102, Australia.
Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Bentley, Perth, WA 6102, Australia.
Int J Mol Sci. 2023 Mar 8;24(6):5202. doi: 10.3390/ijms24065202.
(), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host's immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB-the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years-reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in .
结核分枝杆菌()是导致结核病(TB)的病原体,是一种顽固的病原体,在全球广泛存在,潜伏感染全球约四分之一的人口。当宿主的免疫系统减弱时,休眠细菌的无症状状态会升级为可传播的、活跃的形式。目前,针对药物敏感(DS)菌株的一线治疗方案是 6 个月的四联药物治疗方案,需要严格遵守以避免复发和耐药。贫困、难以获得适当的治疗以及患者不遵医嘱是导致更为严重的耐药(DR)菌株出现的原因,与一线方案相比,这些菌株需要更长的治疗时间,使用毒性更大、更昂贵的药物。在过去十年中,只有三种新药,贝达喹啉(BDQ)和两种硝基咪唑衍生物德拉马尼(DLM)和丙硫脒(PMD)被批准用于治疗结核病,这是 50 多年来市场上推出的第一种具有新作用模式的抗结核病药物,反映了新抗结核病药物的开发和批准的淘汰率。本文将讨论结核病的发病机制、当前的治疗方案以及对结核病控制工作的挑战。本综述还旨在强调最近被确定为有前途的临床前和临床抗结核病药物候选物的几种小分子,这些小分子抑制中的新蛋白靶标。