title: Synthesis and antitumor activities of novel α-aminophosphonates dehydroabietic acid derivatives.
abstract: A series of novel α-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma cell), HepG2 (human liver cancer cell) and SKOV3 (human ovarian cancer cell) human cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The pharmacological screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-FU. The action mechanism of representative compound 7c was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound can induce cell apoptosis in NCI-H460 cells. Cell cycle analysis showed that compound 7c mainly arrested NCI-H460 cells in G1 stage.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Chemical Engineering of Guangxi Normal University, Guilin 541004, Guangxi, PR China.
authors.forename: Xiao-Chao
authors.initials: XC
authors.lastname: Huang
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Pan
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Tian
authors.forename: Heng-Shan
authors.initials: HS
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D045784:Abietanes; D000970:Antineoplastic Agents; D063065:Organophosphonates; C013913:dehydroabietic acid
keywords: Aminophosphonate; Apoptosis; Cell cycle; Cytotoxicity; Dehydroabietic acid