Journal of Asian Natural Products Research p. 272 - 298 (2017)
Update date:2022-08-03
Topics:
Huang, Bao-Zhan
Xin, Guang
Ma, Li-Mei
Wei, Ze-Liang
Shen, Yan
Zhang, Rui
Zheng, Hua-Jie
Zhang, Xiang-Hua
Niu, Hai
Huang, Wen
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.
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