title: 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.affiliation: Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhan
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Jia
authors.forename: Daocheng
authors.initials: D
authors.lastname: Wu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: Xu