title: Synthesis and biological evaluation of novel aniline-derived asiatic acid derivatives as potential anticancer agents.
abstract: Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, (1)H NMR and (13)C NMR. In vitro antitumor activities of all compounds against MGC-803, NCI-H460, HepG2, Hela and 7404 cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The new compounds 5a-5t showed stronger anti-proliferative activity than AA, especially compound 5b was found to be the best inhibition activity on HepG2 cell line. In addition, the mechanism of compound 5b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, flow cytometric, qRT-PCR (quantitative real-time PCR) and Western blot. Compound 5b induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis showed that compound 5b mainly arrested HepG2 cells in G1 stage.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Li
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Ri-Zhen
authors.initials: RZ
authors.lastname: Huang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Gui-Yang
authors.initials: GY
authors.lastname: Yao
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Man-Yi
authors.initials: MY
authors.lastname: Ye
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China. Electronic address: whengshan@163.com.
authors.forename: Heng-Shan
authors.initials: HS
authors.lastname: Wang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China. Electronic address: panym2013@hotmail.com.
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Pan
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Jing-Teng
authors.initials: JT
authors.lastname: Xiao
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; C017032:asiatic acid; C023650:aniline
keywords: Anilines; Apoptosis; Asiatic acid; Cytotoxicity; Synthesis