title: Synthesis, characterization, and biological studies of diosgenyl analogs.
abstract: A series of diosgenyl analogs were prepared from diosgenin to evaluate their anticancer activity and antithrombotic property. Analog 4, which had a spiroketal structure with a 6-aminohexanoic acid residue, exhibited the highest potency against all five tumor cell lines. It significantly blocked tumor growth, induced cell apoptosis and autophagy, and regulated cellular calcium concentration, mitochondrial membrane potential, adenosine triphosphate, and cell cycle. In addition, fluorescence-tagged compounds indicated that the analogs could rapidly accumulate in the cytoplasm, but no specific localization in the nucleus of cancer cells was observed. Furthermore, preliminary structure-activity relationship studies demonstrated that spiroketal analogs exhibit better antithrombotic activity than furostanic analogs, which exhibit the opposite effect by promoting thrombosis. Our study indicates that compound 4 may be a promising anticancer drug candidate for cancer patients with thromboembolism.
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.
authors.forename: Bao-Zhan
authors.initials: BZ
authors.lastname: Huang
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.
authors.forename: Guang
authors.initials: G
authors.lastname: Xin
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.|b Regenerative Medicine Research Center , West China Hospital, Sichuan University, Chengdu 610041 , China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Ma
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.
authors.forename: Ze-Liang
authors.initials: ZL
authors.lastname: Wei
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.|b Regenerative Medicine Research Center , West China Hospital, Sichuan University, Chengdu 610041 , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.|b Regenerative Medicine Research Center , West China Hospital, Sichuan University, Chengdu 610041 , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.|c Department of Integrated Traditional Chinese and Western Medicine , West China Hospital, Sichuan University , Chengdu 610041 , China.
authors.forename: Hua-Jie
authors.initials: HJ
authors.lastname: Zheng
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.|d Institute of Sort Science , Sichuan University , Chengdu 610041 , China.
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.|e College of Mathematics , Sichuan University , Chengdu 610041 , China.
authors.forename: Hai
authors.initials: H
authors.lastname: Niu
authors.affiliation: a Laboratory of Ethnopharmacology , Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University , Chengdu 610041 , China.|b Regenerative Medicine Research Center , West China Hospital, Sichuan University, Chengdu 610041 , China.|c Department of Integrated Traditional Chinese and Western Medicine , West China Hospital, Sichuan University , Chengdu 610041 , China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013923:Thromboembolism / Q000188:drug therapy
chemical_list: D004144:Diosgenin; D002118:Calcium
keywords: Diosgenin; antithrombosis; antitumor; diosgenyl analog