ABSTRACT
Thiazolidinones, synthesized from multicomponent reactions of 2-heteroarylmethylamine, arenealdehydes and mercaptoacetic acid, have been tested against six yeasts, namely Candida albicans, C. parapsilosis, C. guilliermondii, Cryptococcus laurentii, Trichosporon asahii and Rhodotorula spp. The activities were expressed as minimum inhibitory concentrations (MIC) and the minimum fungicidal concentrations (MFC). The most affected yeasts were Rhodotorula spp and T. asahii. The cytotoxicities of the thiazolidinones against the fibroblast 3T3/NIH cell line are also described. The antifungal results and the low cytotoxicity of the compounds in this work provide good guides for the further development of active compounds.
Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Fibroblasts/drug effects , Rhodotorula/drug effects , Thiazolidines/pharmacology , Trichosporon/drug effects , Animals , Antifungal Agents/chemistry , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Mice , Microbial Sensitivity Tests , Molecular Structure , NIH 3T3 Cells , Structure-Activity Relationship , Thiazolidines/chemistryABSTRACT
A series of sixteen novel thiazolidinone derivatives were synthesized from the efficient one-pot reaction of 2-(piperidin-1-yl)ethylamine, arenealdehydes and mercaptoacetic acid in good yields. Identification and characterization of products were achieved by NMR and GC-MS techniques. The in vitro antifungal activities of all synthesized compounds were evaluated against seven fungi: Candida albicans, Candida parapsilosis, Candida guilliermondii, Cryptococcus laurentii, Geotrichum sp, Trichosporon asahii and Rhodotorula sp. The results are expressed as the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) and the best results were found against the Rhodotorula sp yeast. Two thiazolidinones (4h and 4l), MIC and MFC (16.5 µg/mL) proved to be 1.6 times more active than fluconazole and four of them (4b, 4e, 4g and 4k (MIC and MFC 25 µg/mL)) showed similar activity of standard drug to Rhodotorula sp. In addition, the cytotoxicity of thiazolidinones 4a-p was evaluated on cultured Vero cells and most of them displayed low toxicity (above 98 µg/mL). These preliminary and important results could be considered a starting point for the development of new antifungal agents.
