Novel Triazole-Linked Xanthine-Steroid Hybrids: Molecular Docking and In Vitro Evaluation Against α-Glucosidase and MCF-7 Cells.

Triazole hybrids have emerged as versatile scaffolds exhibiting diverse pharmacological profiles. In this study, four novel xanthine steroid hybrids linked via a 1,2,3-triazole moiety (4-7) were efficiently synthesized through copper(I)-catalyzed azide alkyne cycloaddition. Their bioactive potential was investigated using molecular docking and in vitro assays targeting both metabolic and apoptotic pathways. Docking simulations were performed against the anti-apoptotic protein BCL-2 (isoform 1), associated with human breast adenocarcinoma cells, and α-glucosidase, a key enzyme involved in carbohydrate hydrolysis. Among the series, compound 4 displayed the highest binding affinity toward α-glucosidase and significant affinity toward BCL-2. In vitro assays confirmed that compound 4 exhibited the most potent dual effect, demonstrating α-glucosidase inhibition with an IC50 value of 123.9 µM (95% CI: 119-129 µM) and an antiproliferative effect on MCF-7 cells, reaching a maximum viability reduction of 21% ± 3% at 250 µM. The dual activity is largely attributed to the 1,2,3-triazole linker, which facilitates stacking and critical hydrogen-bonding interactions with its biological targets.