THE IN-VITRO ACTIVITIES OF NOVEL BENZOXAZINORIFAMYCINS AGAINST MYCOBACTERIUM-LEPRAE

The activities of four newly synthesized benzoxazinorifamycin derivati ves, either alone or in combination with ofloxacin, against strains of Mycobacterium leprae were determined by assessing their effects on tw o biochemical parameters of metabolic activity which served as surroga te markers for growth in vitro. KRM-1648 and KRM-2312 were the most ac tive agents tested against both a rifampicin-susceptible isolate (MICs of 0.05 and 0.1 mg/L respectively) and a rifampicin-resistant isolate (MICs of 0.2 and 0.3 mg/L respectively); both compounds were more act ive than either rifampicin or rifabutin. The activities of the two oth er derivatives, KRM-1657 and KRM-1668, against a rifampicin-susceptibl e strain (MICs of 0.3 mg/L) were similar to that of rifampicin, while the MIC of each of these agents for the rifampicin-resistant strain wa s 1.0 mg/L. In common with rifabutin, both of the more active derivati ves demonstrated synergy with ofloxacin against the rifampicin-suscept ible isolates. The results of this study suggest that these compounds, in combination with ofloxacin as part of multidrug regimens, warrant further evaluation as treatment for patients with leprosy.