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J Med Chem ; 64(8): 4359-4395, 2021 04 22.
Article in English | MEDLINE | ID: mdl-33826327

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.


Subject(s)
Antitubercular Agents/chemistry , Extensively Drug-Resistant Tuberculosis/pathology , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Ciprofloxacin/chemistry , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Disease Progression , Drug Carriers/chemistry , Drug Evaluation, Preclinical , Drug Resistance, Bacterial/genetics , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/immunology , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Streptomycin/chemistry , Streptomycin/pharmacology , Streptomycin/therapeutic use , Structure-Activity Relationship , Thiophenes/chemistry , Thiophenes/pharmacology , Thiophenes/therapeutic use , Toll-Like Receptors/metabolism
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