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解锁 InhA:抑制结核分枝杆菌的新方法。

Unlocking InhA: Novel approaches to inhibit Mycobacterium tuberculosis.

机构信息

Department of Chemical Sciences, I.K. Gujral Punjab Technical University, Kapurthala, India.

University Institute of Pharmaceutical Sciences and Research, Baba Farid University of Health Sciences, Faridkot, Punjab 151203, India.

出版信息

Bioorg Chem. 2024 May;146:107250. doi: 10.1016/j.bioorg.2024.107250. Epub 2024 Mar 5.

Abstract

Multidrug-resistant tuberculosis continues to pose a health security risk and remains a public health emergency. Antimicrobial resistance result from treatment regimens that are both insufficient and incomplete leading to the emergence of multidrug-resistant tuberculosis, extensively drug-resistant tuberculosis and totally drug-resistant tuberculosis. The impact of tuberculosis on the people suffering from HIV (Human immunodeficiency virus infection) have resulted in the increased research efforts in designing and discovery of novel antitubercular drugs that may result in decreasing treatment duration, minimising the need for multiple drug intake, minimising cytotoxicity and enhancing the mechanism of action of drug. While many drugs are available to treat tuberculosis, a precise and timely cure is still absent. Consequently, further investigation is needed to identify more recent molecular equivalents that have the potential to swiftly remove this disease. Isoniazid (INH), a treatment for tuberculosis (TB), targets the enzyme InhA (mycobacterium enoyl acyl carrier protein reductase), the Mycobacterium tuberculosis enoyl-acyl carrier protein (ACP) reductase, most common INH resistance is circumvented by InhA inhibitors that do not require KatG (catalase-peroxidase) activation, as a result, researchers are trying to work in the area of development of InhA inhibitors which could help in eradicating the era of tuberculosis from the world.

摘要

耐多药结核病继续构成健康安全风险,仍然是公共卫生紧急情况。抗生素耐药性是由于治疗方案既不充分也不完全导致出现耐多药结核病、广泛耐药结核病和完全耐药结核病。结核病对艾滋病毒(人类免疫缺陷病毒感染)患者的影响导致了设计和发现新型抗结核药物的研究工作增加,这可能导致治疗时间缩短、减少多种药物的摄入、降低细胞毒性和增强药物作用机制。虽然有许多药物可用于治疗结核病,但仍缺乏精确和及时的治愈方法。因此,需要进一步研究以确定更近期的分子等价物,这些分子等价物有可能迅速消除这种疾病。异烟肼(INH)是一种治疗结核病(TB)的药物,其作用靶点是酶 InhA(分枝杆菌烯酰酰基辅酶 A 还原酶),是结核分枝杆菌烯酰酰基辅酶 A (ACP)还原酶,最常见的 INH 耐药性是通过不需要 KatG(过氧化氢酶-过氧化物酶)激活的 InhA 抑制剂来规避的,因此,研究人员正试图在开发 InhA 抑制剂领域开展工作,这有助于从世界上消除结核病时代。

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