title: Design, synthesis and anticancer activity evaluation of novel C14 heterocycle substituted epi-triptolide.
abstract: Two series of novel C14 heterocycle substituted epi-triptolide derivatives as potential anticancer agents were synthesized and tested for their cytotoxicity against SKOV-3 and PC-3 tumor cell lines. The introduction of C14β-aryl heterocycle aminomethyl substituent to the leading compound was found to be an effective modification method to retain the potent anticancer activity. Meanwhile, the series of epi-triptolide derivatives (21-40) with C14α-hydroxyl group, still retained the natural product's cytotoxicity. This is apparently challenges the classical structure-activity relationship of triptolide that considers the C14β-hydroxyl group to be essential for its anticancer activity.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Tang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.
authors.forename: Huijin
authors.initials: H
authors.lastname: Feng
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China. Electronic address: ycli@mail.shcnc.ac.cn.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D004852:Epoxy Compounds; D006571:Heterocyclic Compounds; D010616:Phenanthrenes; C001899:triptolide
keywords: Anticancer; Heterocycle; PC-3; SKOV-3; Synthesis; Triptolide