Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review

被引:31
作者
Angula, Klaudia T. [1 ]
Legoabe, Lesetja J. [1 ]
Beteck, Richard M. [1 ]
机构
[1] North West Univ, Ctr Excellence Pharmaceut Sci Pharmacen, ZA-2520 Potchefstroom, South Africa
关键词
tuberculosis; drug development; pharmacokinetics; fluoroquinolones; diarylquinolines; nitroimidazoles; EARLY BACTERICIDAL ACTIVITY; KILL MYCOBACTERIUM-TUBERCULOSIS; MULTIPLE-DOSE PHARMACOKINETICS; TRANSFER-RNA SYNTHETASE; IN-VIVO ACTIVITIES; MULTIDRUG-RESISTANT; COMBINATION THERAPY; LEAD OPTIMIZATION; CLINICAL-TRIALS; BIOLOGICAL EVALUATION;
D O I
10.3390/ph14050461
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a curable airborne disease currently treated using a drug regimen consisting of four drugs. Global TB control has been a persistent challenge for many decades due to the emergence of drug-resistant Mtb strains. The duration and complexity of TB treatment are the main issues leading to treatment failures. Other challenges faced by currently deployed TB regimens include drug-drug interactions, miss-matched pharmacokinetics parameters of drugs in a regimen, and lack of activity against slow replicating sub-population. These challenges underpin the continuous search for novel TB drugs and treatment regimens. This review summarizes new TB drugs/drug candidates under development with emphasis on their chemical classes, biological targets, mode of resistance generation, and pharmacokinetic properties. As effective TB treatment requires a combination of drugs, the issue of drug-drug interaction is, therefore, of great concern; herein, we have compiled drug-drug interaction reports, as well as efficacy reports for drug combinations studies involving antitubercular agents in clinical development.
引用
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页数:45
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