title: Design, synthesis and in vitro evaluation of novel ursolic acid derivatives as potential anticancer agents.
abstract: A series of novel ursolic acid (UA) derivatives modified at the C-3 and the C-28 positions were designed and synthesized in an attempt to develop potential antitumor agents. The in vitro cytotoxicity were evaluated against five cancer cell lines (MGC-803, HCT-116, T24, HepG2 and A549 cell lines) and a normal cell (HL-7702) by MTT assay. The screening results indicated that some of these target compounds displayed moderate to high levels of antiproliferative activities compared with ursolic acid and 5-fluorouracil (5-FU), and exhibited much lower cytotoxicity than 5-FU, indicating that the targeted compounds had selective and significant effect on the cell lines. The induction of apoptosis and affects on the cell cycle distribution of compound 6r were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which revealed that the antitumor activity of 6r was possibly achieved through the induction of cell apoptosis by G1 cell-cycle arrest. Western blot and qRT-PCR (quantitative real-time PCR) experiments demonstrated that compound 6r may induce apoptosis through both of intrinsic and extrinsic apoptosis pathway.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors.forename: Shi-Xian
authors.initials: SX
authors.lastname: Hua
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, 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 Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, 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 Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
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 Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, 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 Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China; Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Xinyi Road 15, Guangxi 541001, PR China. Electronic address: zhangye81@126.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China. Electronic address: whengshan@163.com.
authors.forename: Heng-Shan
authors.initials: HS
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D020169:Caspases; D017382:Reactive Oxygen Species; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Antitumor; Apoptosis; Piperazine-thiourea; Ursolic acid derivatives