Pregnenolonyl-α-glucoside exhibits marked anti-cancer and CYP17A1 enzymatic inhibitory activities

Abstract

We report here that pregnenolonyl-α-glucoside (2), a steryl glycoside synthesized directly from pregnenolone and glucose via a consecutive multienzyme-catalyzed process, exhibits marked dose-dependent cytotoxic activity against HT29, AGS, and ES-2 cells with IC₅₀ values of 23.5 to 50.9 μM. An in vitro CYP17A1 binding pattern assay and protein–ligand docking model support that 2, like abiraterone, binds in the active site heme iron pocket of CYP17A1.