title: [In vitro synergisms among hydrazones, ajoeno and posaconazole against Cryptococcus spp].
abstract: The aim of this study was to assess the in vitro susceptibility to novel antifungal compounds, the steroidal hydrazones, and to compare their antifungal activity and synergistic effects with other compounds, such as ajoeno and posaconazole on Cryptocococus spp isolates. Three Cryptococcus strains were used for this study (42794, 4050 and 44192) and their antifungal sensitivity and synergistic effects with ajoeno and posaconazole were evaluated according to the CLSI protocol number M27-A2. Candida albicans (ATCC 90028) and Candida parapsilosis (ATCC 22019) were used as controls. A plateau effect with hydrazones (H1, H2, H3, H4) was observed after 10 microM (CMI). However, with H4 only a mild inhibition on the growth was obtained. Combining hydrazone and ajoeno, CMI values between 25 and 50 microM were obtained. The highest inhibitions values were obtained with posaconazole and a CMI value of 6 microM for the strains 42794 and 44192, and a CMI value of 20 microM for the strain 4050. Synergy was observed combining posaconazole with ajoeno, ajoeno with hydrazone 3 and posaconazole with hydrazone 3. Fractional inhibitory concentrations were 0.24, 0.16 and 0.09 respectively, which might indicate a synergistic effect. Important synergistic effects were obtained with posaconazole and ajoeno, ajoeno and hydrazone 3 and posaconazole with hydrazone 3, which would be very useful for clinical trials in the future.
authors.affiliation: Laboratorio de Fisicoquímica de Parásitos, Instituto de Biología Experimental (IBE), Facultad de Ciencias, Universidad Central de Venezuela.
authors.forename: Julio
authors.initials: J
authors.lastname: Vivas
authors.forename: Primavera
authors.initials: P
authors.lastname: Alvarado
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Visbal
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alvarez-Aular
authors.forename: Egle
authors.initials: E
authors.lastname: Ruiz
authors.forename: Eliades
authors.initials: E
authors.lastname: Ledezma
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D056285:Cryptococcus gattii / Q000187:drug effects*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D006835:Hydrazones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D013454:Sulfoxides; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D004220:Disulfides; D006835:Hydrazones; D013454:Sulfoxides; D014230:Triazoles; C101425:posaconazole; C048980:ajoene