Antimycobacterial activity of diospyrin and its derivatives against Mycobacterium aurum

Abstract

The objective of this study was to determine the antimycobacterial activity of diospyrin (D1) and four of its derivatives (D2, D5, D7 and D17) against the non-pathogenic Mycobacterium aurum. The effect of these compounds was determined on growth parameters and drug efflux pumping activity. Diospyrin was shown to be the most active in inhibiting the growth of M. aurum whilst D2 was inactive. D17 was found to have the lowest MIC of < 0.1 µg/ml, while the MIC of other compounds were found to be as follows: D1= 0.1 µg/ml, D5= 0.39 µg/ml, D7= 0.78 µg/ml and D2 =3.13 µg/ml, in order of potency. The compounds were bacteriostatic rather than bactericidal as the MBCs were greater than 50 µg/ml. The compounds were potent efflux pump inhibitors as D5 enhanced ciprofloxacin accumulation by 160 %, D17 by 58 %, D7 by 41 %, D1 by 37 % when compared with the standard efflux pump inhibitor, reserpine, which enhanced accumulation by 51 %. D2 had no effect on drug efflux pumping activity. The modifications of diospyrin enhanced the activity of D17 and D5 by decreasing the MIC and enhancing accumulation of ciprofloxacin, respectively. In contrast, activity decreased significantly for D2 in the growth and accumulation assays. Diospyrin and its derivatives are potential antimycobacterial agents and drug efflux inhibitors and could be used to enhance the activity of known antimycobacterial agents that are actively effluxed from M. tuberculosis.