title: The conversion of oridonin to spirolactone-type or enmein-type diterpenoid: synthesis and biological evaluation of ent-6,7-seco-oridonin derivatives as novel potential anticancer agents.
abstract: Starting from commercial available natural product oridonin (1), a practical synthesis of ent-6,7-seco-oridonin derivatives (2, 3, 5, and 9) was accomplished and their biological activities were evaluated. The conversion of spirolactone-type diterpenoid to enmein-type was first completed. The results demonstrated that all synthesized ent-6,7-seco-oridonin derivatives could markedly inhibit the proliferation of cancer cells. Compared with Taxol, the most cytotoxic compound 5 has similar potency in A549 cell and slightly less cytotoxicity in Bel-7402 cell. Compound 5 was also more potent than parent compound oridonin in mice with MGC-803 gastric cancer in vivo. Then a series of novel 14-O-derivatives of 5 were further designed and synthesized, which showed better activity than 5 and similar activity as Taxol in vitro. The structure-activity relationships of oridonin derivatives were also discussed in the present investigations.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
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: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jieyun
authors.initials: J
authors.lastname: Jiang
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D004224:Diterpenes / Q000737:chemistry*; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020014:K562 Cells; D051379:Mice; D013148:Spironolactone / Q000737:chemistry*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D045786:Diterpenes, Kaurane; C011959:oridonin; D013148:Spironolactone; C007594:enmein