Efficient microwave-assisted prenylation of pinostrobin and biological evaluation of its derivatives as antitumor agents

• Published in: Bioorganic & medicinal chemistry letters 2010-04, Vol.20 (7), p.2086-2089
• Main Authors: Poerwono, Hadi, Sasaki, Shigeru, Hattori, Yoshiyuki, Higashiyama, Kimio
• Format: Article
• Language: English
• Subjects: 5-Hydroxy-7-methoxyflavanone; Anticancer activity; Antineoplastic agents; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Biological and medical sciences; Cell Line, Tumor; Claisen rearrangement; Cross-metathesis; Drug Screening Assays, Antitumor; Flavanones - chemistry; Flavanones - isolation & purification; Flavanones - pharmacology; General aspects; Humans; Inhibitory Concentration 50; Medical sciences; Microwave-assisted reaction; Microwaves; Mitsunobu reaction; Neoplasms - drug therapy; Pharmacology. Drug treatments; Prenylation; Zingiberaceae - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.02.068

Pinostrobin ( 1) was converted to its prenylated or allylated derivatives ( 2– 8) using a microwave reactor. All resulting compounds showed cytotoxic activity toward a panel of human tumor cell lines with significantly lower IC 50 (μM) values than compound 1. Pinostrobin (5-hydroxy-7-methoxyflavanone) obtained in relatively large amounts from fingerroot ( Boesenbergia pandurata) was converted to its C-6 and C-8 prenylated derivatives. The Mitsunobu reaction, europium(III)-catalyzed Claisen–Cope rearrangement, and Claisen reaction coupled with cross-metathesis were used as the key steps. Using a sealed-vessel microwave reactor, the Mitsunobu and Claisen/Cope reactions occurred smoothly with short reaction times and in satisfactory yields. The target compounds and five new intermediary substances showed cytotoxic activity toward SK-BR-3, MCF-7, PC-3, and Colo-320DM human tumor cell lines, and all of them had significantly lower IC 50 (μM) values than pinostrobin.