Clinical Microbiology and PK/PD Division, Indian Institute of Integrative Medicine (IIIM), Campus, Sanat Nagar, Srinagar, Jammu & Kashmir 190005, India; Academy of Scientific and Innovative Research (AcSIR), CSIR- Indian Institute of Integrative Medicine (IIIM), Campus, Sanat Nagar, Srinagar, Jammu & Kashmir 190005, India.
Clinical Microbiology and PK/PD Division, Indian Institute of Integrative Medicine (IIIM), Campus, Sanat Nagar, Srinagar, Jammu & Kashmir 190005, India; Department of Biochemistry, University of Kashmir, Srinagar, Jammu & Kashmir 190006, India.
Biomed Pharmacother. 2017 Nov;95:1520-1534. doi: 10.1016/j.biopha.2017.09.036. Epub 2017 Sep 21.
Tuberculosis is the leading infectious disease responsible for an estimated one and a half million human deaths each year around the globe. HIV-TB coinfection and rapid increase in the emergence of drug resistant forms of TB is a dangerous scenario. This underlines the urgent need for new drugs with novel mechanism of action. A plethora of literature exist that highlight the importance of enzymes involved in the biosynthesis of mycobacterial cell wall responsible for its survival, growth, permeability, virulence and resistance to antibiotics. Therefore, assembly of cell wall components is an attractive target for the development of chemotherapeutics against Mycobacterium tuberculosis. The aim of this review is to highlight novel sets of enzyme inhibitors that disrupt its cell wall biosynthetic pathway. These include the currently approved first and second line drugs, candidates in clinical trials and current structure activity guided endeavors of scientific community to identify new potent inhibitors with least cytotoxicity and better efficacy against emergence of drug resistance till date.
结核病是全球每年导致约 150 万人死亡的主要传染病。HIV-TB 合并感染和耐药形式的结核病迅速出现是一种危险的情况。这凸显了迫切需要具有新作用机制的新药。大量文献强调了参与分枝杆菌细胞壁生物合成的酶的重要性,这些酶负责其生存、生长、渗透性、毒力和对抗生素的耐药性。因此,细胞壁成分的组装是开发针对结核分枝杆菌的化学治疗药物的有吸引力的目标。本综述的目的是强调破坏其细胞壁生物合成途径的新型酶抑制剂。这些包括目前批准的一线和二线药物、临床试验中的候选药物以及科学界目前基于结构活性的努力,以确定具有最低细胞毒性和对耐药性出现更好疗效的新型有效抑制剂。