A novel C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis

Bokolia, NP and Bag, K and Sarkar, B and Jhawar, R and Chatterji, D and Jayaraman, N and Ghosh, A (2024) A novel C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis. In: Tuberculosis, 149 .

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Abstract

Mycobacterium tuberculosis is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. The present study investigates the use of C-4 modified isotetrones as bio-enhancers. A series of studies suggest an isotetrone, labeled as C11, inhibits growth, improves MIC, MBC and enhances the killing of M. tuberculosis H37Rv strain when used in combination with the first line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduces the generation of spontaneous mutants against rifampicin and reaches a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds are effective against the MDR strain of M. tuberculosis and non-cytotoxic in HepG2 cells. We find that C11 induces the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy. © 2024 Elsevier Ltd

Item Type:	Journal Article
Publication:	Tuberculosis
Publisher:	Elsevier
Additional Information:	The copyright for this article belongs to Elsevier
Keywords:	amikacin; ascorbic acid; bioenhancer; ethambutol; isoniazid; isotetrone; kanamycin; moxifloxacin; reactive oxygen metabolite; rifampicin; streptomycin; tamoxifen; tuberculostatic agent; unclassified drug, animal cell; antibacterial activity; Article; bacterial strain; bactericidal activity; bacteriostatic activity; controlled study; dose response; drug efficacy; drug potency; Hep-G2 cell line; human; human cell; in vitro study; intracellular killing; macrophage; minimum bactericidal concentration; minimum inhibitory concentration; multidrug resistance; multidrug resistant bacterium; Mycobacterium tuberculosis; nonhuman; oxidation reduction state; rifampicin resistance; spontaneous mutation
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Chemical Sciences > Organic Chemistry
Date Deposited:	30 Oct 2024 06:28
Last Modified:	30 Oct 2024 06:28
URI:	http://eprints.iisc.ac.in/id/eprint/86536

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