Click chemistry inspired facile synthesis and bioevaluation of novel triazolyl analogs of D-(+)-pinitol

Abstract

Cu (I)-catalyzed alkyne–azide cycloaddition was carried out for the preparation of novel 1,4-disubstituted 1,2,3-triazoles of D-(+)-pinitol. All the analogs were screened for cytotoxicity against promyelocytic leukemia (HL-60), colorectal carcinoma (HCT 116) and pancreatic carcinoma (Mia-Paca-2) cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay. Compounds 2, 3 and 7 showed the best activity with IC50 of 19.2, 17.5 and 16.4 μM against leukemia (HL-60), colorectal carcinoma (HCT 116) and pancreatic carcinoma (Mia-Paca-2) cell lines respectively. All the triazolyl analogs were further evaluated for β-glucosidase inhibitory activity, wherein, the deprotected derivatives: 6a, 18a and 25a showed better activity with IC50 of 148.5, 139.2 and 142.4 μM respectively. The structure activity relationship (SAR) studies revealed that the analogs with bromo, nitro or methyl groups in R (substituted phenyl moiety attached to 1,2,3-triazole) moiety exhibited better cytotoxicity, while as, the analogs with N-substituted long chain aliphatic hydrocarbon R moieties displayed effective β-glucosidase inhibition. Keywords: D-(+)-pinitol, Click chemistry, Triazole, Cytotoxicity, β-glucosidases inhibition