title: Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells.
abstract: A series of novel spirolactone-type diterpenoid derivatives of oridonin (12a-j) were designed and synthesized. All the target compounds showed improved anti-proliferative activity against a panel of human cancer cell lines and the most effective compound 12j was more potent than positive control Taxol in K562 and Bel-7402 cells with IC(50) values of 0.39 μM and 1.39 μM, respectively. The cellular mechanisms showed that compound 12j induced apoptosis at low micromolar concentrations in human hepatoma Bel-7402 cells. These results demonstrate that the spirolactone-type diterpenoid derivatives of oridonin have optimized growth inhibitory activity against cancer cells and interesting apoptosis-inducing ability.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Dahong
authors.initials: D
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.forename: Bowen
authors.initials: B
authors.lastname: Jiang
authors.forename: Guyue
authors.initials: G
authors.lastname: Liu
authors.forename: Yuetong
authors.initials: Y
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Sun
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy*; D008958:Models, Molecular; D017239:Paclitaxel / Q000627:therapeutic use; D013148:Spironolactone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D045786:Diterpenes, Kaurane; C011959:oridonin; D013148:Spironolactone; C002627:kaurene; D017239:Paclitaxel