The activities of four newly synthesized
benzoxazinorifamycin derivatives, either alone or in combination with
ofloxacin, against strains of Mycobacterium leprae were determined by assessing their effects on two biochemical parameters of metabolic activity which served as
surrogate markers for growth in vitro.
KRM-1648 and KRM-2312 were the most active 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 active than either
rifampicin or
rifabutin. The activities of the two other derivatives,
KRM-1657 and
KRM-1668, against a
rifampicin- susceptible 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 was 1.0mg/L. In common with
rifabutin, both of the more active derivatives demonstrated synergy with
ofloxacin against the
rifampicin-susceptible 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.