Targeting Tuberculosis: Novel Scaffolds for Inhibiting Cytochrome bd Oxidase,Journal of Chemical Information and Modeling

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Targeting Tuberculosis: Novel Scaffolds for Inhibiting Cytochrome bd Oxidase
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2024-06-14 , DOI: 10.1021/acs.jcim.4c00344
Christian Seitz ₁ , Surl-Hee Ahn ₂ , Haixin Wei ₁ , Matson Kyte ₃ , Gregory M Cook ₃ , Kurt L Krause ₄ , J Andrew McCammon _{1,

5}

Affiliation

Discovered in the 1920s, cytochrome bd is a terminal oxidase that has received renewed attention as a drug target since its atomic structure was first determined in 2016. Only found in prokaryotes, we study it here as a drug target for Mycobacterium tuberculosis (Mtb). Most previous drug discovery efforts toward cytochrome bd have involved analogues of the canonical substrate quinone, known as Aurachin D. Here, we report six new cytochrome bd inhibitor scaffolds determined from a computational screen and confirmed on target activity through in vitro testing. These scaffolds provide new avenues for lead optimization toward Mtb therapeutics.

中文翻译：

靶向结核病：抑制细胞色素 bd 氧化酶的新型支架

细胞色素bd于 20 年代被发现，是一种末端氧化酶，自 2016 年首次确定其原子结构以来，作为药物靶点再次受到关注。仅在原核生物中发现，我们在这里将其作为结核分枝杆菌( Mtb ) 的药物靶点进行研究。之前大多数针对细胞色素bd的药物发现工作都涉及经典底物醌的类似物，称为 Aurachin D。在这里，我们报告了六种新的细胞色素bd抑制剂支架，这些支架是通过计算筛选确定的，并通过体外测试确认了目标活性。这些支架为Mtb治疗的先导化合物优化提供了新途径。

更新日期：2024-06-14

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