title: Novel 3',5'-diprenylated chalcones inhibited the proliferation of cancer cells in vitro by inducing cell apoptosis and arresting cell cycle phase.
abstract: A double Claisen rearrangements synthetic strategy was established for the total synthesis of 4,4'-dimethyl medicagenin (compound 6c). A series of its analogs also were prepared, including two novel 3',5'-diprenylated chalcones, in which ring B was replaced by azaheterocycle. The structures of the twenty-two newly synthesized compounds were confirmed by1H NMR,13C NMR and ESI-MS. In vitro, the cytotoxicity of the target compounds was evaluated using cancer cells. Noticeably, compound 10 exhibited broad-spectrum cytotoxicity on PC3 prostate cancer cells, MDA-MB-231 breast cancer cells (MDA), HEL and K562 erythroleukemia cells with IC50values of 2.92, 3.14, 1.85 and 2.64 μM, respectively. Further studies indicated that compound 10 induced apoptosis and arrested the cell cycle phase of the above mentioned four cancer cell lines. By contrast, compound 6g selectively displayed potent inhibitory activity against the proliferation of HEL cells with an IC50value of 4.35 μM. Compound 6g slightly induced apoptosis and arrested cell cycle phase of HEL cells. Preliminary structure-activity relationship studies indicated that, in all cancer cell lines evaluated, the 3-pyridinyl group was essential for cytotoxicity.
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China; School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, PR China.
authors.forename: Zhonghang
authors.initials: Z
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China; School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, PR China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China.
authors.forename: Zhanxing
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China; School of Pharmaceutical Sciences, Guizhou University, Guiyang 550025, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, PR China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Liang
authors.affiliation: Guizhou Provincial People's Hospital, Guiyang 550002, PR China. Electronic address: doctorzhujianguo@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China. Electronic address: luohengzz@sina.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, PR China. Electronic address: bixue_xu@126.com.
authors.forename: Bixue
authors.initials: B
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D054876:Prenylation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones
keywords: Cell apoptosis; Cell cycle arrest; Cytotoxicity; Diprenylated chalcones