title: Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]pyrimidine derivatives bearing arylmethylene hydrazine moiety.
abstract: Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a-f, 13a-k and 15a-h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC(50)values of 0.003 µM, 0.42 µM and 0.74 µM, which was 1.6- to 290-fold more potent than GDC-0941.
authors.affiliation: Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Wufu
authors.initials: W
authors.lastname: Zhu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhai
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.forename: Mei
authors.initials: M
authors.lastname: Bai
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D006834:Hydrazines