Design and synthesis of a gossypol derivative with improved antitumor activities.

Abstract

A novel chemical process has been devised for the synthesis of a new derivative of gossypol, 6,7,6',7'-tetrahydroxy-5,5'-diisopropyl-3,3'-dimethyl-[2,2']binaphthalenyl-1,4,1',4'-tetraone (Apogossypolone). This new process has only four steps, with a shorter synthesis span, a simple purification process, and improved yield and quality. The structure of apogossypolone was characterized by( 1)H-nuclear magnetic resonance, (13)C-nuclear magnetic resonance, mass spectroscopy, infrared spectroscopy, and elemental analysis. Cell-cytotoxicity assay demonstrates that apogossypolone is three- to six-fold more potent than the parent compound, (-)-gossypol, in inhibiting the human prostate tumor cell lines PC-3 and DU-145 as well as the human breast cancer cell line MDA-MB-231. The colony-formation assay with DU-145 cells showed that apogossypolone inhibited more than 70% of colony formation at 1 muM, whereas (-)-gossypol at 10 muM only inhibited less than 50% of colony formation. The results indicate that apogossypolone exerts strong antitumor activities in human prostate and breast cancer cells, and thus represents a promising cancer therapeutic.

• Authors: Yonghua Zhan, Guangfeng Jia, Daocheng Wu, Yiqing Xu, Liang Xu
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 342 Issue 4 Pg. 223-9 (Apr 2009) ISSN: 1521-4184 [Electronic] Germany
• PMID: 19340835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents, Phytogenic
• Indicators and Reagents
• Tetrazolium Salts
• Thiazoles
• thiazolyl blue
• Gossypol

Topics

• Antineoplastic Agents, Phytogenic (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Colony-Forming Units Assay
• Drug Screening Assays, Antitumor
• Gossypol (analogs & derivatives, chemical synthesis, pharmacology)
• Humans
• Indicators and Reagents
• Models, Molecular
• Tetrazolium Salts
• Thiazoles