A facile 'click' approach to novel 15β-triazolyl-5α-androstane derivatives, and an evaluation of their antiproliferative activities in vitro.

Intermolecular Cu(I)-catalyzed azide-alkyne cycloadditions of 15β-azido-17β-hydroxy-5α-androstan-3β-yl acetate with different terminal alkynes under optimized reaction conditions were carried out to furnish 15β-triazolyl derivatives in good yields. Subsequent oxidation of the 'click' products with the Jones reagent afforded the corresponding 17-ketones. All the synthetized compounds were tested on three malignant human cell lines (HeLa, MCF7 and A431) in order to investigate their antiproliferative activities in vitro. Evidence of cell cycle blockade and apoptosis induction was obtained for the most effective five selected compounds by means of flow cytometry and microscopic techniques. The 15β-triazolyl-5α-androstane framework may be considered an appropriate base for the design of steroidal antiproliferative agents.