IN-VITRO AND IN-VIVO RESULTS OF BRODIMOPRIM AND ANALOGS ALONE AND IN COMBINATION AGAINST ESCHERICHIA-COLI AND MYCOBACTERIA

New diaminodiphenylsulfone inhibitors of dihydropteroate synthase are described with increased inhibitory activity against mycobacteria and plasmodia, whereas their side effect of methemoglobin formation could be suppressed. The optimization of diaminobenzylpyrimidines, inhibitor s of dihydrofolate reductase, led to derivatives with increased inhibi tory effect against mycobacteria, especially M. leprae and plasmodia. Some of these derivatives show autosynergism. Finally the combination of brodimoprim (BDP) and dapsone (DDS) was developed for the treatment of leprosy. First clinical trials in Paraguay and Ethiopia show that combinations of BDP/DDS and BDP/DDS plus rifampicin were highly effect ive and may become an alternative multi-drug therapy for the treatment of leprosy. The tolerance of the regimens used was generally good.