Mukherjee Raju, Chandra Pal Anup, Banerjee Mousumi
Division of Biology, Indian Institute of Science Education and Research, Karakambadi Road, Tirupati, 517507, India.
Division of Biology, Indian Institute of Science Education and Research, Karakambadi Road, Tirupati, 517507, India.
Tuberculosis (Edinb). 2017 Sep;106:44-52. doi: 10.1016/j.tube.2017.06.004. Epub 2017 Jun 30.
Management of tuberculosis, already a global health emergency, is becoming increasingly challenging with extensive misuse of second line drugs and their inaccessibility to eighty percent of the eligible patients. Rising statistics of antimicrobial resistance underscores the need for a set of completely new and more effective class of compounds with novel mechanisms of action that can be administered in combination to replace and shorten the present intensive six months regimen. In this review, we stress on the importance and the successes of phenotypic screening for discovery of anti-mycobacterial compound and discuss the importance of performing secondary screens and counter screens to get early estimate on compound's potentials for a successful development. We also highlight the recent advances and the related caveats in the assays that have been developed and discuss new screening modalities that can be incorporated during hit-selection to gain a quick insight into the mechanism of action, thus enabling quicker decisions in a hit triage.
结核病的管理已然是一场全球卫生紧急事件,随着二线药物的广泛滥用以及80%的符合条件患者无法获取这些药物,其管理正变得愈发具有挑战性。抗菌药物耐药性统计数据的不断上升凸显了对一类全新且更有效的化合物的需求,这类化合物具有新颖的作用机制,可联合使用以替代并缩短目前为期六个月的强化治疗方案。在本综述中,我们强调了表型筛选在发现抗分枝杆菌化合物方面的重要性和成功之处,并讨论了进行二次筛选和反筛选以尽早评估化合物成功开发潜力的重要性。我们还突出了已开发检测方法的最新进展及相关注意事项,并讨论了在命中选择过程中可纳入的新筛选模式,以便快速洞察作用机制,从而在命中物分类中做出更快决策。