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结核病:近十年中免疫反应、疾病进展以及药物化学方面的研究进展概述,旨在开发针对广泛耐药结核菌株的潜在药物。

Tuberculosis: An Overview of the Immunogenic Response, Disease Progression, and Medicinal Chemistry Efforts in the Last Decade toward the Development of Potential Drugs for Extensively Drug-Resistant Tuberculosis Strains.

机构信息

Department of Biophysics, Panjab University, Chandigarh 160014, India.

UIPS, Panjab University, Chandigarh 160014, India.

出版信息

J Med Chem. 2021 Apr 22;64(8):4359-4395. doi: 10.1021/acs.jmedchem.0c01833. Epub 2021 Apr 7.

Abstract

Tuberculosis (TB) is a slow growing, potentially debilitating disease that has plagued humanity for centuries and has claimed numerous lives across the globe. Concerted efforts by researchers have culminated in the development of various strategies to combat this malady. This review aims to raise awareness of the rapidly increasing incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, highlighting the significant modifications that were introduced in the TB treatment regimen over the past decade. A description of the role of pathogen-host immune mechanisms together with strategies for prevention of the disease is discussed. The struggle to develop novel drug therapies has continued in an effort to reduce the treatment duration, improve patient compliance and outcomes, and circumvent TB resistance mechanisms. Herein, we give an overview of the extensive medicinal chemistry efforts made during the past decade toward the discovery of new chemotypes, which are potentially active against TB-resistant strains.

摘要

结核病(TB)是一种缓慢发展的、潜在致残的疾病,困扰了人类几个世纪,在全球范围内夺走了无数人的生命。研究人员的共同努力最终促成了各种对抗这种疾病的策略的发展。本综述旨在提高人们对耐多药(MDR)和广泛耐药(XDR)结核病发病率迅速上升的认识,强调了过去十年中在结核病治疗方案中引入的重大改变。描述了病原体-宿主免疫机制的作用以及预防疾病的策略。为了减少治疗时间、提高患者的依从性和治疗效果、避免结核病耐药机制,人们一直在努力开发新的药物疗法。在此,我们概述了过去十年中为发现可能对耐药结核菌株有效的新型化学型而进行的广泛药物化学研究工作。

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