title: Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and 'click' strategy.
abstract: To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluations against HepG2, Caski and HeLa cell lines, three steroidal triazoles 5b, 5f and 5m in this library were found to possess potent anti-proliferative effects against Caski cells with the half-inhibitory concentrations (IC50) of 9.4-11.8 μM. The high-efficient and straightforward process was attractive feature for facile preparation of anti-tumor steroidal triazoles.
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Lu
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, PR China. Electronic address: hny115@126.com.
authors.forename: Nian-Yu
authors.initials: NY
authors.lastname: Huang
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, PR China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: He
authors.affiliation: State Key Laboratory of Molecular Reaction Dynamics, Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Science, 457 Zhongshan Road, Dalian 116023, PR China.
authors.forename: Wei-Qiao
authors.initials: WQ
authors.lastname: Deng
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, PR China. Electronic address: kzou@ctgu.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Zou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D004144:Diosgenin / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013150:Spirostans / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D013150:Spirostans; D014230:Triazoles; D003300:Copper; D004144:Diosgenin
keywords: (25R)-Spirostan-1,4,6-triene-3-one; Click chemistry; Cytotoxic activities; Epoxide ring-opening reaction; Steroidal triazoles