Anti-tuberculosis lead molecules from natural products targeting Mycobacterium tuberculosis ClpC1

Nov 21, 2015Journal of industrial microbiology & biotechnology

Natural compounds targeting a key protein in tuberculosis bacteria

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Abstract

New anti-TB compounds cyclomarin A, lassomycin, and ecumicin demonstrate potent activity against multidrug-resistant and extensively drug-resistant M. tb.

The emergence of multidrug-resistant and extensively drug-resistant M. tb presents a major public health challenge.
Existing anti-TB drugs have lost effectiveness against these resistant strains.
Cyclomarin A, lassomycin, and ecumicin are cyclic peptides that have shown strong anti-TB activity in laboratory settings.
These compounds target ClpC1, a crucial protein for M. tb growth.
A comparison with currently approved anti-TB drugs is provided to evaluate their potential as therapeutic agents.

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Tuberculosis (TB) is a serious and potentially fatal disease caused by Mycobacterium tuberculosis (M. tb). The occurrence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tb is a significant public health concern because most of the anti-TB drugs that have been in use for over 40 years are no longer effective for the treatment of these infections. Recently, new anti-TB lead compounds such as cyclomarin A, lassomycin, and ecumicin, which are cyclic peptides from actinomycetes, have shown potent anti-TB activity against MDR and XDR M. tb as well as drug-susceptible M. tb in vitro. The target molecule of these antibiotics is ClpC1, a protein that is essential for the growth of M. tb. In this review, we introduce the three anti-TB lead compounds as potential anti-TB therapeutic agents targeting ClpC1 and compare them with the existing anti-TB drugs approved by the US Food and Drug Administration.

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