Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and 'click' strategy

Abstract

To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluations against HepG2, Caski and HeLa cell lines, three steroidal triazoles 5b, 5f and 5m in this library were found to possess potent anti-proliferative effects against Caski cells with the half-inhibitory concentrations (IC50) of 9.4-11.8 μM. The high-efficient and straightforward process was attractive feature for facile preparation of anti-tumor steroidal triazoles.

Keywords: (25R)-Spirostan-1,4,6-triene-3-one; Click chemistry; Cytotoxic activities; Epoxide ring-opening reaction; Steroidal triazoles.