title: In vitro and in vivo results of brodimoprim and analogues alone and in combination against E. coli and mycobacteria.
abstract: 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, inhibitors of dihydrofolate reductase, led to derivatives with increased inhibitory 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 effective and may become an alternative multi-drug therapy for the treatment of leprosy. The tolerance of the regimens used was generally good.
authors.affiliation: Institute for Experimental Biology and Medicine, Borstel, Germany.
authors.forename: J K
authors.initials: JK
authors.lastname: Seydel
mesh_terms: D003622:Dapsone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D004927:Escherichia coli Infections / Q000188:drug therapy; D006801:Humans; D007918:Leprosy / Q000188:drug therapy; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology; D009164:Mycobacterium Infections / Q000188:drug therapy; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014295:Trimethoprim / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D003622:Dapsone; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; C037079:brodimoprim