Multidrug-resistant cancer cell susceptibility to cytotoxic quassinoids, and cancer chemopreventive effects of quassinoids and canthin alkaloids.

Abstract

Twenty-three quassinoids (1-23), which were isolated previously from Simaroubaceous plants, were evaluated for cytotoxicity against three multidrug-resistant cancer cell lines, KB-VIN, KB-7d, and KB-CPT. Nine compounds (2-7 and 9-11) showed significant cytotoxicity in all three cell lines. Compounds 1, 12-14, 17, and 20 demonstrated significant activity against the KB-7d and KB-CPT cell lines, and compounds 18, 19, and 23 revealed notable activity only against KB-7d cells. Structure-activity relationships were drawn based on these data. In addition, six quassinoid derivatives (24-29) and four canthin alkaloids (30-33), which were isolated from Brucea antidysenterica, were examined for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation as cancer chemopreventive agents. All of these compounds demonstrated significant inhibitory effects against EBV-EA activation.

• Authors: Chihiro Murakami, Narihiko Fukamiya, Sadaaki Tamura, Masayoshi Okano, Kenneth F Bastow, Harukuni Tokuda, Teruo Mukainaka, Hoyoky Nishino, Kuo-Hsiung Lee
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 12 Issue 18 Pg. 4963-8 (Sep 15 2004) ISSN: 0968-0896 [Print] England
• PMID: 15336275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Alkaloids
• Cytotoxins
• Quassins

Topics

• Alkaloids (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Chemoprevention (methods)
• Cytotoxins (chemistry, isolation & purification, pharmacology)
• Drug Resistance, Multiple (drug effects, physiology)
• Drug Resistance, Neoplasm (drug effects, physiology)
• Humans
• Quassins (chemistry, isolation & purification, pharmacology)