Abstract
Tuberculosis is one of the world’s deadliest infectious disease with 1.5 millions deaths annually. It is imperative to discover novel compounds with potent activity against M. tuberculosis. In this study, susceptibilities of M. smegmatis to the octahedral ruthenium(II) polypyridyl complexes, 1 {[(bpy)3Ru] (PF6)2 (bpy = 2,2′-bipyridine)}, 2 {[(phen)2Ru(dppz)](PF6)2 (phen = 1,10-phenanthroline, dppz = dipyridophenazine)} and 3 {[(phen)3Ru](PF6)2} were measured by broth microdilution and reported as the MIC values. Toxicities of complex 3 to LO2 and hepG2 cell lines were also measured. Complex 2 inhibited the growth of M. smegmatis with MIC value of 2 µg/mL, while complex 3 was bactericidal with MIC value of 26 µg/mL. Furthermore, the bactericidal activity of complex 3 was dependent on reactive oxygen species production. Complex 3 showed no cytotoxicity against LO2 and hepG2 cell lines at concentration as high as 64 µg/mL, paving the way for further optimization and development as a novel antibacterial agent for the treatment of M. tuberculosis infection.
Highlights
Tuberculosis (TB) affects 9.6 million people each year and leads to 1.5 millions deaths annually, which is exacerbated by the emergence of multidrug resistance (Engstrom, 2016; Glaziou et al, 2014)
In order to gain novel antibacterial agents for the treatment of M. tuberculosis infection, we investigated the antibacterial activities of the representative ruthenium polypyridyl complexes, 1, 2 and 3 (Fig. 1), and found that they displayed potent antimicrobial activity against M. smegmatis, a nonpathogenic strain often used as a surrogate for the detection of compounds which are inhibitory to the growth of M. tuberculosis (Chaturvedi et al, 2007; Kostova, 2006)
Bacteria were grown in TSB medium; C. neoformans and C. albicans were grown in Yeast Extract Peptone Dextrose (YPD) medium; M. smegmatis mc2 155 was grown in 7H9 liquid medium (Difco) supplemented with 0.05% w/v Tween 80, 0.5% glycerol and 0.5% glucose or were grown on 7H10 agar supplemented with 1% glycerol and 0.5% glucose
Summary
Tuberculosis (TB) affects 9.6 million people each year and leads to 1.5 millions deaths annually, which is exacerbated by the emergence of multidrug resistance (Engstrom, 2016; Glaziou et al, 2014). It is extremely desired to develop novel classes of antibacterial compounds with new mode of action to avoid existing resistance to established targets. Due to the success of cis-platinum anticancer agents, there has been considerable interest in the development of therapeutic agents based upon other transition metals and ruthenium(II) complexes in particular, because of their well known interaction with nucleic acids, which are generally believed to be a target for many metal-based drugs (Abid, Shamsi & Azam, 2016; Madureira et al, 2013).
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