The antiparasite effects of cyclosporin A: possible drug targets and clinical applications.
1. The immunosuppressive drug cyclosporin A, and some of its nonimmunosuppressive derivatives, are potent inhibitors of a range of parasites of humans. 2. Cyclosporin A and the structurally unrelated immunosuppressant FK506 are known to act on T-lymphocytes as complexes with their binding proteins, cyclophilins and FKBPs, respectively. 3. Cyclophilins and FKBPs have been structurally identified in a number of parasites and, in some instances, are believed to play roles in the antiparasitic actions of these drugs. 4. Nonimmunosuppressive cyclosporins and FK506 derivatives may have clinical potential in certain parasitic diseases, especially malaria and schistosomiasis, and identification of the targets of these drugs in parasites may lead to development of novel chemotherapeutic agents.
Bell
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Dept of Microbiology, Moyne Institute, Trinity College, Dublin 2, Ireland.
Roberts
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Chappell
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D000591:Amino Acid Isomerases / Q000502:physiology; D000977:Antiparasitic Agents / Q000494:pharmacology*; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology; D020123:Sirolimus; D013329:Structure-Activity Relationship; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
D000977:Antiparasitic Agents; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D011090:Polyenes; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus