Antileishmanial effects of clofazimine and other antimycobacterial agents.
In the search for more effective alternatives to the presently-used antileishmanial drugs, the activity of the major groups of antimycobacterial compounds has been examined, both in vitro and in animal models of infection. In vitro, clofazimine was the most active compound tested, with a mean ED50 of 2.3 mg l-1 against Leishmania mexicana amazonensis, 1.4 mg l-1 against L. donovani and 0.5 mg l-1 against L. major. Other active compounds were the thiosemicarbazone, thiambutosine, and salinazid, a derivative of isoniazid. Isoniazid itself was inactive, and rifampicin only partially active. In vivo, only clofazimine displayed significant activity, and it was most effective against the cutaneous infections. It is concluded that antimycobacterial activity is in general a poor predictor of antileishmanial potency.
Evans
A T
AT
Department of Medical Protozoology, London School of Hygiene and Tropical Medicine, U.K.
Croft
S L
SL
Peters
W
W
Neal
R A
RA
D000287:Administration, Topical; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D002991:Clofazimine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007891:Leishmania / Q000187:drug effects*; D007893:Leishmania donovani / Q000187:drug effects; D007894:Leishmania mexicana / Q000187:drug effects; D007895:Leishmania tropica / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000995:Antitubercular Agents; D002991:Clofazimine