title: Diamidines as antitrypanosomal, antileishmanial and antimalarial agents.
abstract: Diamidine-containing compounds have a long history of use in the treatment of African trypanosomiasis and leishmaniasis. The discovery that diamidine prodrugs possess in vivo antimicrobial activity when administered orally has led to a renewed interest in this class of compounds for the treatment of parasitic infections. In this review, the selectivity of diamidines against trypanosomes, Leishmania and Plasmodium is rationalized through mechanism-of-action studies. An overview of the antiprotozoal activities of newer diamidines and diamidine prodrugs is also presented, along with a summary of the progress made toward the clinical development of new diamidines for use against these parasitic diseases.
authors.affiliation: The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Columbus 43210-1291, USA. werbovetz.1@osu.edu
authors.forename: Karl
authors.initials: K
authors.lastname: Werbovetz
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001550:Benzamidines / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000254:growth & development; D007896:Leishmaniasis / Q000188:drug therapy; D016778:Malaria, Falciparum / Q000188:drug therapy; D010419:Pentamidine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014347:Trypanosoma brucei gambiense / Q000187:drug effects / Q000254:growth & development; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000188:drug therapy
chemical_list: D000962:Antimalarials; D000981:Antiprotozoal Agents; D001550:Benzamidines; D011355:Prodrugs; D014344:Trypanocidal Agents; D010419:Pentamidine; C033286:furamidine; C458513:pafuramidine