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新型分枝杆菌细胞壁抑制剂对抗耐药结核病研发的最新进展

Recent Progress in the Development of Novel Mycobacterium Cell Wall Inhibitor to Combat Drug-Resistant Tuberculosis.

作者信息

Belete Tafere Mulaw

机构信息

Department of Pharmacology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

出版信息

Microbiol Insights. 2022 May 23;15:11786361221099878. doi: 10.1177/11786361221099878. eCollection 2022.

Abstract

Despite decades of research in drug development against TB, it is still the leading cause of death due to infectious diseases. The long treatment duration, patient noncompliance coupled with the ability of the tuberculosis bacilli to resist the current drugs increases multidrug-resistant tuberculosis that exacerbates the situation. Identification of novel drug targets is important for the advancement of drug development against . The development of an effective treatment course that could help us eradicates TB. Hence, we require drugs that could eliminate the bacteria and shorten the treatment duration. This review briefly describes the available data on the peptidoglycan component structural characterization, identification of the metabolic pathway, and the key enzymes involved in the peptidoglycan synthesis, like -Acetylglucosamine-1-phosphate uridyltransferase, mur enzyme, alanine racemase as well as their inhibition. Besides, this paper also provides studies on mycolic acid and arabinogalactan synthesis and the transport mechanisms that show considerable promise as new targets to develop a new product with their inhibiter.

摘要

尽管在抗结核药物研发方面进行了数十年的研究,但结核病仍是传染病致死的主要原因。治疗周期长、患者不依从,再加上结核杆菌对现有药物的耐药能力,导致耐多药结核病增加,使情况更加恶化。确定新的药物靶点对于推进抗结核药物研发至关重要。开发有效的治疗方案有助于我们根除结核病。因此,我们需要能够消灭细菌并缩短治疗周期的药物。本综述简要介绍了有关肽聚糖成分结构表征、代谢途径的确定以及肽聚糖合成中涉及的关键酶(如N-乙酰葡糖胺-1-磷酸尿苷转移酶、mur酶、丙氨酸消旋酶)及其抑制作用的现有数据。此外,本文还提供了关于分枝菌酸和阿拉伯半乳聚糖合成以及转运机制的研究,这些研究作为开发具有抑制剂的新产品的新靶点显示出了巨大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed5e/9131376/11a44835f28b/10.1177_11786361221099878-fig1.jpg

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