Saha Pallavi, Das Samarpita, Indurthi Harish K, Kumar Rohit, Roy Arnab, Kalia Nitin Pal, Sharma Deepak K
Department of Pharmaceutical Engg. and Tech, IIT-Banaras Hindu University Varanasi UP 221005 India
Department of Pharmacology and Toxicology, NIPER-Hyderabad Hyderabad 500037 India.
RSC Med Chem. 2024 Jan 27;15(3):769-787. doi: 10.1039/d3md00587a. eCollection 2024 Mar 20.
Cytochrome (cyt-) oxidase, one of the two terminal oxidases in the () oxidative phosphorylation pathway, plays an indispensable role in maintaining the functionality of the metabolic pathway under stressful conditions. However, the absence of this oxidase in eukaryotic cells allows researchers to select it as a potential drug target for the synthesis of anti-tubercular (anti-TB) molecules. Cyt- inhibitors have often been combined with cytochrome / super-complex inhibitors in anti-TB drug regimens to achieve a desired bactericidal response. The functional redundancy between both the terminal oxidases is responsible for this. The cryo-EM structure of cyt- oxidase from (PDB ID: 7NKZ) further accelerated the research to identify its inhibitor. Herein, we have summarized the reported anti-TB cyt- inhibitors, insight into the rationale behind targeting cyt- oxidase, and an outline of the architecture of cyt- oxidase.
细胞色素(cyt-)氧化酶是呼吸链()氧化磷酸化途径中的两种末端氧化酶之一,在应激条件下维持代谢途径的功能方面发挥着不可或缺的作用。然而,真核细胞中缺乏这种氧化酶,这使得研究人员能够将其选为合成抗结核(anti-TB)分子的潜在药物靶点。在抗结核药物治疗方案中,cyt-抑制剂通常与细胞色素/超复合物抑制剂联合使用,以实现理想的杀菌效果。这是由于两种末端氧化酶之间的功能冗余所致。来自结核分枝杆菌的cyt-氧化酶的冷冻电镜结构(PDB ID:7NKZ)进一步加速了寻找其抑制剂的研究。在此,我们总结了已报道的抗结核cyt-抑制剂,深入探讨了靶向cyt-氧化酶背后的原理,以及结核分枝杆菌cyt-氧化酶的结构概述。