title: The effects by neuroleptics, antimycotics and antibiotics on disulfide reducing enzymes from the human pathogens Acanthamoeba polyphaga and Naegleria fowleri.
abstract: This paper discusses the effects of two neuroleptic agents, chlorpromazine and trifluoperazine; three antimycotics, amphotericin B, ketoconazole and miconazole and four antibiotics, pentamidine, rifampicin, mepacrine and metronidazole on the NADPH-dependent disulfide reducing enzymes cystine reductase (CysR), glutathione reductase (GR) trypanothione reductase (TR) and a putative disulfide reductase for compound X in Acanthamoeba polyphaga from the human pathogens A. polyphaga and Naegleria fowleri. Against A. polyphaga, all nine drugs studied had the capacity to inhibit the putative disulfide reductase from the trophozoites at a concentration of 32microg/ml during a 24h incubation and they were: the neuroleptics trifluoperazine (100%) and chlorpromazine (96%), the antimycotics miconazole (89%) ketoconazole (81%) and amphotericin B, (53%) and the antibiotics pentamidine (89%), rifampicin (64%), mepacrine (57%) and metronidazole (14%). Only six of the nine drugs simultaneously inhibited CysR, GR and the putative disulfide reductase. In N. fowleri, the most potent inhibitors of trypanothione reductase were amphotericin B and miconazole which inhibited 100% at a concentration of 32microg/ml during the 24h incubation followed by the neuroleptics trifluoperazine (92%) and chlorpromazine (80%) and the antibiotic mepacrine (70%). All these also inhibited CysR and GR from the trophozoites other than mepacrine which inhibited only CysR and TR. Ketoconazole, rifampicin (which did not affect CysR), pentamidine and metronidazole had opposite effects since they did not inhibit but increased the amount of the three thiols.
authors.affiliation: Center of Research on Infectious Diseases, National Institute of Public Health, Cuernavaca, Mor. 62508, Mexico. ondarza@servidor.unam.mx
authors.forename: Raúl N
authors.initials: RN
authors.lastname: Ondarza
authors.forename: Angélica
authors.initials: A
authors.lastname: Iturbe
authors.forename: Eva
authors.initials: E
authors.lastname: Hernández
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects* / Q000378:metabolism; D016848:Naegleria fowleri / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D014150:Antipsychotic Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; C019976:Cystine reductase; D005980:Glutathione Reductase