Antifungal activity, SAR and physicochemical correlation of some thiazole-1,3,5-triazine derivatives

Objective. - Present research communication was towards the investigation of antifungal minimum inhibitory concentration (MIC) and minimum fingicidal concentration (MFC) activity of some substituted clubbed thiazole-1,3,5-triazines derivatives and effect of physicochemical properties on bioactivity. Material and methods. - MIC and MFC were evaluated against Candida albicans, Candida glabrata, Cryptococcus neoformans and Aspergillus niger using modified microdilution method recommended by CLSI. Cytotoxicity was determinate on the viability of marine shrimp larvaes. SAR and physicochemical correlations were studied by Molinspiration software. Results. - The 5 and 9 derivatives showed an excellent antifungal activity with MIC lower than fiuconazole and equivalent to amphotericin B specially against C. albicans and C. glabrata. The toxicity of these two derivatives was non-existent for 5 and moderate for 9 at the used concentration. SAR study around prototype molecule suggests that presence of di-hydrophobic fragment on 1,3,5-triazine is necessary for antifungal activity than halogen substituted aromatic amine. Conclusion. - On the basis of selectivity, potency and non-toxicity, we have obtained two molecules (5 and 9) as prospective leads for further research work on 1,3,5-triazine as antifungal drug. (C) 2011 Elsevier Masson SAS. All rights reserved.