Synthesis and antitumor activity of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives

A series of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives, have been designed and synthesized in nine steps starting from ursodeoxycholic acid. The in vitro antitumor activity of the target compounds has been evaluated against HCT-116, MCF-7, K562, and SGC-7901 cell lines. The pharmacological results showed that most of the prepared compounds display excellent selective cytotoxicity toward HCT-116, MCF-7, and K562 cell lines. Particularly, compounds 10c, 10f and 10g show high inhibitory activity on these human cancer cell lines (IC50: 2.39–9.34 μM). Conversely, all compounds are generally inactive against SGC-7901, with only 10b having IC50 below 50 μM.

Graphical abstractA series of N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, ursodeoxycholic acid derivatives, were synthesized and evaluated in vitro antitumor activity against HCT-116, MCF-7, K562, and SGC-7901 cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Ursodeoxycholic acid derivatives, N-sulfonyl-3,7-dioxo-5β-cholan-24-amides, were designed and synthesized. ► The in vitro antitumor activity was evaluated against four cancer cell lines. ► Three active compounds show high inhibitory activity on three human cancer cell lines.