title: Synthesis and pharmacological evaluation of the novel pseudo-symmetrical tamoxifen derivatives as anti-tumor agents.
abstract: Four pseudo-symmetrical tamoxifen derivatives, RID-B (13), RID-C (14), RID-D (15), and bis(dimethylaminophenetole) (16), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of these pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 13 and 16 strongly inhibit the viability of the HL-60 human acute promyelocytic leukemia cell line, whereas 14 possesses a medium activity against the same cell line and 15 has no effect on the cell viability. The global anti-tumor activity of 13-16 against a variety of human cancer cells was assessed using a panel of 39 human cancer cell lines (JFCR 39), and it was shown that RID-B (13) strongly inhibited the growth of several cancer cell lines at concentrations of less than 1 microM (at 0.38 microM for SF-539 [central nervous system], at 0.58 microM for HT-29 [colon], at 0.20 microM for DMS114 [lung], at 0.21 microM for LOX-IMVI [melanoma], and at 0.23 microM for MKN74 [stomach]).
authors.affiliation: Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. shiina@rs.kagu.tus.ac.jp
authors.forename: Isamu
authors.initials: I
authors.lastname: Shiina
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sano
authors.forename: Kenya
authors.initials: K
authors.lastname: Nakata
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Akane
authors.initials: A
authors.lastname: Sasaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ikekita
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Nagahara
authors.forename: Yoshimune
authors.initials: Y
authors.lastname: Hasome
authors.forename: Takao
authors.initials: T
authors.lastname: Yamori
authors.forename: Kanami
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen