Synthesis of the new pseudo-symmetrical tamoxifen derivatives and their anti-tumor activity.
Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-60 human acute promyelocytic leukemia, whereas 16 possesses medium activity against the cell line and 17 has no effect on the cell viability. The agarose gel electrophoresis for DNA cleavage showed the cell death might be induced by apoptosis.
Shiina
Isamu
I
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. shiina@rs.kagu.tus.ac.jp
Sano
Yoshiyuki
Y
Nakata
Kenya
K
Kikuchi
Takaaki
T
Sasaki
Akane
A
Ikekita
Masahiko
M
Hasome
Yoshimune
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D018922:HL-60 Cells; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013997:Time Factors
D000970:Antineoplastic Agents; D013629:Tamoxifen