Search for newer antileprosy drugs.
In 1991 World Health Organization proclaimed the goal of global elimination of leprosy as a public health problem by year 2000 by implementing multidrug therapy (MDT). Since then the prevalence rate has declined by 85%. However, during the same period the incidence rate of leprosy has remained constant or even has been increasing. This suggests that it will take a long time for the eradication of leprosy and that without in-vitro cultivation of M. leprae, eradication of leprosy is not likely to be achieved. While in-vitro cultivation is a long-term goal, as an immediate measure, there is an urgent need for the development of newer drugs and newer multidrug therapy regimens. Using the in-vitro system for screening potential antileprosy drugs and also using the mouse foot-pad system we have evaluated several compounds in four classes of drugs--dihydrofolate reductase inhibitors, fluoroquinolones, rifampicin analogues and phenazines--and identified at least two compounds that appear to be more potent than dapsone, rifampicin and clofazimine. Newer combinations of rifampicin analogues and fluoroquinolones have also been identified that seem to be better than the combination of rifampicin and ofloxacin.
Department of Biological Sciences, Florida Institute of Technology, Melbourne 32901, USA.
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D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D024841:Fluoroquinolones; D005493:Folic Acid Antagonists / Q000494:pharmacology; D005528:Foot / Q000382:microbiology; D006801:Humans; D007917:Leprostatic Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000254:growth & development; D010619:Phenazines / Q000494:pharmacology; D012293:Rifampin / Q000031:analogs & derivatives / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D005493:Folic Acid Antagonists; D007917:Leprostatic Agents; D010619:Phenazines; D013762:Tetrahydrofolate Dehydrogenase; D012293:Rifampin