title: Synthesis and biological evaluation of novel sarsasapogenin derivatives as potential anti-tumor agents.
abstract: Based on the fact that timosaponin A-III (TA-III) exhibits potent cytotoxic effects and has been considered as a potential anti-tumor agent, a range of novel sarsasapogenin derivatives 1, 2a-2g, 3, 4, 5, 6a-6g have been synthesized by a simple and facile synthetic route. The in vitro cytotoxic activity of these synthetic compounds has been evaluated against ten human cancer cell lines. The pharmacological results showed that most of the sarsasapogenin derivatives displayed excellent selective cytotoxicity toward the cancer cell lines. An amino group at C-3 or C-26 position of the sapogenin had a profound influence on the cytotoxic activity. In particular, compound 6c exhibited significantly inhibitory activity against A375-S2 (IC50=0.56μM) and HT1080 (IC50=0.72μM) cells. However, introducing a bromo or morpholinyl substituent at the C-3 and C-26 position of the sapogenin generally rendered it inactive against the human cancer cell lines. This research provides a theoretical reference for the exploration of new anti-tumor drugs.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Xun-Chen
authors.initials: XC
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: sjwang_99@163.com.
authors.forename: Shao-Jie
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Shenyang University of Chemical Technology, Shenyang 110142, People's Republic of China.
authors.forename: Pin-Yi
authors.initials: PY
authors.lastname: Gao
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Li
authors.affiliation: China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Takshi
authors.initials: T
authors.lastname: Ikejima
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: songsj99@163.com.
authors.forename: Shao-Jiang
authors.initials: SJ
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D012502:Sapogenins / Q000138:chemical synthesis / Q000494:pharmacology*; D013150:Spirostans / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012502:Sapogenins; D013150:Spirostans
keywords: 26-Aminofurostan derivatives; 3-Aminospirostan derivatives; Anti-tumor activity; Sarsasapogenin; Spirostan