Polypharmacology-Driven Discovery and Design of Highly Selective, Dual and Multitargeting Inhibitors of Mycobacterium tuberculosis - A Review.

IF 3 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current drug targets Pub Date : 2024-01-01 DOI:10.2174/0113894501306302240526160804

Franklin V Amandy, Gabriel L L Neri, Joe A H Manzano, Adrian D Go, Allan P G Macabeo

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引用次数: 0

Abstract

The increasing demand for novel antitubercular agents has been the main 'force' of many TB research efforts due to the uncontrolled growing number of drug-resistant strains of M. tuberculosis in the clinical setting. Many strategies have been employed to address the drug-resistant issue, including a trend that is gaining attention, which is the design and discovery of Mtb inhibitors that are either dual- or multitargeting. The multiple-target design concept is not new in medicinal chemistry. With a growing number of newly discovered Mtb proteins, numerous targets are now available for developing new biochemical/cell-based assays and computer-aided drug design (CADD) protocols. To describe the achievements and overarching picture of this field in anti- infective drug discovery, we provide in this review small molecules that exhibit profound inhibitory activity against the tubercle bacilli and are identified to trace two or more Mtb targets. This review also presents emerging design methodologies for developing new anti-TB agents, particularly tailored to structure-based CADD.

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多药理学驱动的高选择性、双重和多靶点结核分枝杆菌抑制剂的发现和设计--综述。

由于临床上结核杆菌耐药菌株的数量不受控制地增长，对新型抗结核药物的需求不断增加，这已成为许多结核病研究工作的主要 "动力"。为解决耐药性问题，人们采用了许多策略，其中包括一种日益受到关注的趋势，即设计和发现双靶点或多靶点的结核杆菌抑制剂。多靶点设计概念在药物化学领域并不新鲜。随着新发现的 Mtb 蛋白数量不断增加，现在有许多靶点可用于开发新的生化/细胞检测方法和计算机辅助药物设计（CADD）方案。为了描述这一领域在抗感染药物发现方面取得的成就和总体情况，我们在这篇综述中提供了对结核杆菌具有极强抑制活性的小分子，这些小分子被确定为可追踪两个或多个 Mtb 靶点。本综述还介绍了开发新型抗结核药物的新兴设计方法，特别是基于结构的 CADD。在 Ma.阿莉西亚-阿吉纳尔多（Alicia Aguinaldo）教授七十寿辰。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current drug targets 医学-药学

CiteScore

6.20

自引率

0.00%

发文量

127

审稿时长

3-8 weeks

期刊介绍： Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.