3-O-Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:26

Article

Zhang, Sheng¹  Vue, Bao¹  Huang, Michael¹  Zhang, Xiaojie¹  Lee, Timmy¹  Chen, Guanglin¹  Zhang, Qiang²  Zheng, Shilong²  Wang, Guangdi^2,3  Chen, Qiao-Hong¹ 

[1] Calif State Univ Fresno, Dept Chem, 2555 E San Ramon Ave,M-S SB70, Fresno, CA 93740 USA

[2] Xavier Univ Louisiana, RCMI Canc Res Ctr, 1 Drexel Dr, New Orleans, LA 70125 USA

[3] Xavier Univ Louisiana, Dept Chem, 1 Drexel Dr, New Orleans, LA 70125 USA

关键词: Prostate cancer;    Silibinin;    Cell proliferation;    Cell cycle regulation;    Cell apoptosis;   

DOI  :  10.1016/j.bmcl.2016.05.069

来源: Elsevier

【 摘 要 】

Eight 3-O-alkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin through two synthetic approaches. A one-pot reaction, starting with aerobic oxidation of silibinin followed by direct alkylation of the phenolic hydroxyl group in the subsequent 2,3-dehydrosilibinin, furnishes the desired derivatives in 11-16% yields. The three-step procedure employing benzyl ether to protect 7-OH in silibinin generates the desired derivatives in 30-46% overall yields. The antiproliferative activity of the 2,3-dehydrosilibinin derivatives against both androgen-sensitive and androgen-insensitive prostate cancer cells have been assessed using a WST-1 cell proliferation assay. All derivatives exhibited greater antiproliferative potency than silibinin, with 2,3-dehydrosilibinins each possessing a three-to five-carbon linear alkyl group to 3-OH (IC50 values in a range of 1.71-3.06 mu M against PC-3 and LNCaP cells) as the optimal derivatives. The optimal potency was reached with three-to five-carbon alkyl groups. Our findings suggest that 3-O-propyl-2,3-dehydrosilibinin effectively inhibits the growth of PC-3 prostate cancer cells by arresting cell cycle in the G(0)/G(1) phase, but not by activating PC-3 cell apoptosis. (C) 2016 Elsevier Ltd. All rights reserved.

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