title: The in-vitro activities of novel benzoxazinorifamycins against Mycobacterium leprae.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Florida Institute of Technology, Melbourne 32901-6988, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Dhople
authors.forename: M A
authors.initials: MA
authors.lastname: Ibanez
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D003470:Culture Media; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D007917:Leprostatic Agents / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015242:Ofloxacin / Q000494:pharmacology; D017828:Rifabutin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D012294:Rifamycins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D003470:Culture Media; D007917:Leprostatic Agents; D012294:Rifamycins; D017828:Rifabutin; D000255:Adenosine Triphosphate; D015242:Ofloxacin; D013936:Thymidine; D012293:Rifampin