Natural products and their analogues acting against Mycobacterium tuberculosis: A recent update

Abstract

Tuberculosis (TB) remains one of the deadliest infectious diseases caused by Mycobacterium tuberculosis (M.tb). It is responsible for significant causes of mortality and morbidity worldwide. M.tb possesses robust defense mechanisms against most antibiotic drugs and host responses due to their complex cell membranes with unique lipid molecules. Thus, the efficacy of existing front‐line drugs is diminishing, and new and recurring cases of TB arising from multidrug‐resistant M.tb are increasing. TB begs the scientific community to explore novel therapeutic avenues. A precise knowledge of the compounds with their mode of action could aid in developing new anti‐TB agents that can kill latent and actively multiplying M.tb. This can help in the shortening of the anti‐TB regimen and can improve the outcome of treatment strategies. Natural products have contributed several antibiotics for TB treatment. The sources of anti‐TB drugs/inhibitors discussed in this work are target‐based identification/cell‐based and phenotypic screening from natural products. Some of the recently identified natural products derived leads have reached clinical stages of TB drug development, which include rifapentine, CPZEN‐45, spectinamide‐1599 and 1810. We believe these anti‐TB agents could emerge as superior therapeutic compounds to treat TB over known Food and Drug Administration drugs.

Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation

“…Tuberculosis, one of the oldest known diseases, continues to be a scourge to humans, and despite multiple efforts to control it, about 1.6 million people succumb to the disease every year. [119][120][121] Aminoglycosides such as kanamycin or amikacin are second-line drugs for treating tuberculosis. Unfortunately, numerous M. tuberculosis strains developed resistance to these antibiotics, mainly through the acetyltransferase known as enhanced intracellular survival (Eis).…”

Các hợp chất thứ cấp từ chủng xạ khuẩn actinoplanes missouriensis và hoạt tính ức chế protein ClPC1 của vi khuẩn lao mycobacterium tuberculosis

“…Khác với nhiều loài vi khuẩn khác, ClpC1 ở M. tuberculosis có trình tự bảo toàn cao và khi kết hợp với phức hợp ClpP sẽ đảm nhận vai trò chaperone trong tế bào [5]. Nhiều nghiên cứu đã cho thấy khi ClpC1 mất hoạt tính, sự phân hủy protein trong tế bào bị giảm hoặc có thể bị dừng lại hoàn toàn [6,7]. Do đó, protein ClpC1 đã trở thành mục tiêu quan trọng trong quá trình tìm kiếm và sàng lọc các tác nhân chống lại vi khuẩn lao một cách an toàn và hiệu quả.…”