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

• Published in: Chemical communications (Cambridge, England) England), 2020-02, Vol.56 (11), p.1733-1736
• Main Authors: Chou, Feng-Pai, Hsu, Wen-Chen, Huang, Sheng-Cih, Chang, Chin-Yuan, Chiou, Ya-Sheng, Tsai, Chia-Tse, Lyu, Jason WenJay, Chen, Wei-Ting, Wu, Tung-Kung
• Format: Article
• Language: English
• Subjects: Androstenes - metabolism; Androstenes - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Bacteria - enzymology; Catalytic Domain; Cell Line, Tumor; Cytochrome P-450 Enzyme Inhibitors - chemistry; Cytochrome P-450 Enzyme Inhibitors - metabolism; Cytochrome P-450 Enzyme Inhibitors - pharmacology; Glucosides; Glucosides - chemical synthesis; Glucosides - metabolism; Glucosides - pharmacology; Glycosylation; HEK293 Cells; Humans; Immunoassay; Molecular Docking Simulation; Pregnenolone - analogs & derivatives; Pregnenolone - metabolism; Pregnenolone - pharmacology; Protein Binding; Structural analysis; Toxicity
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c9cc09415f

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 IC 50 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. We report here that pregnenolonyl-α-glucoside ( 2 ) exhibits significant dose-dependent cytotoxicity against HT29, AGS, and ES-2 cells. The biochemical characterization results indicates the putative mechanism of 2 on the catalytic site of CYP17A1.