Synthesis, QSAR and anticandidal evaluation of 1,2,3-triazoles derived from naturally bioactive scaffolds

In the present study, we used eight natural precursors (1a-h) with most of them having promising antimicrobial activities and synthesised their novel 1,2,3-triazole derivatives (3a-h). In the reaction sequences, the precursor compounds (1a-h) were converted to their respective alkyne (2a-h) followed by addition of benzyl azide freshly prepared by the reaction of benzyl bromide with sodium azide using [3 + 2] azide-alkyne cycloaddition strategy. Structural elucidation of all the triazole derivatives was done using FT-IR, H-1, C-13 NMR, mass and elemental analysis techniques. The single crystal X-ray diffraction for 3d was also recorded. The result of in vitro anticandidal activity performed against three different strains of Candida showed that compound 3e was found superior/comparable to fluconazole (FLC) with IC50 values of 0.044 mu g/mL against Candida albicans (ATCC 90028), 12.022 mu g/mL against Candida glabrata (ATCC 90030), and 3.60 mu g/mL against Candida tropicalis (ATCC 750). Moreover, at their IC50 values, compounds 3e and 3h showed <5% hemolysis which indicates the non-toxic behaviour of these inhibitors. Cytotoxicity assay was also performed on VERO cell line and all the derivatives were found nontoxic up to the concentration of 10.0 mu g/mL. The in silico technique of 3D-QSAR was applied to establish structure activity relationship of the synthesized compounds. The results reveal the molecular fragments that play an essential role in improving the anticandidal activity. (C) 2015 Elsevier Masson SAS. All rights reserved.