title: Library construction and biological evaluation of enmein-type diterpenoid analogues as potential anticancer agents.
abstract: A library of promising enmein-type 14-O-diterpenoid derivatives was constructed from a commercially available kaurene-type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel-7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC-803 mice). These results warrant further preclinical investigations of these diterpenoid-based analogues as potential novel anticancer chemotherapeutics.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia St., Nanjing 210009, China.
authors.forename: Dahong
authors.initials: D
authors.lastname: Li
authors.forename: Shengtao
authors.initials: S
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.forename: Lingling
authors.initials: L
authors.lastname: Pei
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Jieyun
authors.initials: J
authors.lastname: Jiang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Sun
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D054852:Small Molecule Libraries