Design and synthesis of O-glycoside derivatives with promising antidiabetic and anticancer potential

Diabetes and cancer are significant global health challenges drawing continuous research efforts for the discovery and development of effective therapeutic agents. Chalcone serves as a fundamental structural component of flavonoids, continuing to fascinate medicinal chemists due to its exceptional biological activities. By implementing glycosylation as a post-synthetic modification, a series of chalcone-O-glucosides were synthesized, alongwith the assessment of their antidiabetic and anticancer potential. In-vitro antidiabetic potential of the glucosides was determined against the α-glucosidase enzyme and most of the compounds exhibited moderate to excellent inhibitory properties which was highest for the compound u92. The cytotoxic properties of the glucosides were examined in Dalton’s Lymphoma cancer cells. One-way ANOVA was used for data analysis at P ≤ 0.05 to validate the results. The compounds u25 and u79 exhibited maximum cytotoxic activity with minimum toxicity to the normal cells. The toxicity of these compounds was evaluated on normal peripheral blood mononuclear cells, enabling a comparative analysis of cellular responses in cancerous versus non-cancerous conditions. ADMET analysis and in silico pharmacophore model generation validated our findings, highlighting these glycosides as promising candidates for further research in developing antidiabetic agents and anticancer drugs targeting the selected cell line.