Abstract
Novel agents are urgently needed to rapidly kill drug-resistant Mycobacterium tuberculosis. Noble metal complexes, particularly polypyridyl iridium complexes serving as therapeutic agents, have attracted considerable interest recently, due to their significant cytotoxic or antimicrobial activities. Here, we reported an polypyridyl iridium dimer complex [Ir(ppy)2Cl]2 (3), with ppy = phenylpyridine, which was found to be active against both exponential growing and non-replicating M. smegmatis, with minimum inhibitory concentration values of 2 μg/mL, and exhibited rapid bactericidal kinetics, killing pathogens within 30–60 min. Moreover, 3 was demonstrated to generate a large amount of reactive oxygen species and to be effective in drug-resistant strains. Taken together, the selectively active iridium(III) dimer complex showed promise for use as a novel drug candidate for the treatment of M. tuberculosis infection.
Highlights
Mycobacterium tuberculosis is an important human pathogen that causes life-threatening infections, claiming around 1.5 million lives each year [1]
Iridium complexes have been extensively explored as anticancer agents due to their unique modular system, the recognition and binding properties of which can be varied by ligand-exchange reactions [10,11,12,13,14]
The results showed that 3 could be used as a rapidly killing agent, killing agent, and the bactericidal effect of 3 on M. smegmatis was owing to Reactive Oxygen Species (ROS) production
Summary
Mycobacterium tuberculosis is an important human pathogen that causes life-threatening infections, claiming around 1.5 million lives each year [1]. Karpin and co-workers reported that iridium complexes with hydrophobic L-amino acids have antibiotic activity against Mycobacterium spp. These reported iridium complexes serving as antimicrobial agents suffer from limitations with respect to their high MIC values, and their possessing bacteriostatic, rather than bactericidal, Polymers 2018, 10, 297; doi:10.3390/polym10030297 www.mdpi.com/journal/polymers. Mycobacterium smegmatis is a fast-growing and non-pathogenic organism closely related to M. Mycobacterium smegmatis is a fast-growing and non-pathogenic organism closely related to tuberculosis. They share vital physiological features, such as dormancy and regulation mechanisms.
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