title: Chiral gossypol derivatives: evaluation of their anticancer activity and molecular modeling.
abstract: To better use gossypol to find promising anticancer compounds, a series of new and known bis-Schiff base analogs of chiral gossypol were synthesized, and their anticancer activity on HeLa, U87 and M85 cells was tested. The results showed that through a simple chemical modification, less active (+)-gossypol could be converted into more active derivatives. When compared with (-)-gossypol, many more potent compounds that could be the promising anticancer agents were found, and some of them were more potent than the anticancer drug Cisplatin against all three cancer cell lines. By eliminating target functional groups, we observed that the major contributor to the anticancer activity of chiral gossypol seemed to be the phenolic groups, and not the aldehyde groups. Through comprehensive analysis of chiral gossypol analogs, the structure-activity relationships were elaborated.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.forename: Haixia
authors.initials: H
authors.lastname: Jiang
authors.forename: Xingxin
authors.initials: X
authors.lastname: Cao
authors.forename: Huiyun
authors.initials: H
authors.lastname: Zhao
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Cui
authors.forename: Biao
authors.initials: B
authors.lastname: Jiang
mesh_terms: D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006072:Gossypol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism; D012545:Schiff Bases / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012545:Schiff Bases; D006072:Gossypol