Synthesis and pharmacological evaluation of the novel pseudo-symmetrical tamoxifen derivatives as anti-tumor agents

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 μM (at 0.38 μM for SF-539 [central nervous system], at 0.58 μM for HT-29 [colon], at 0.20 μM for DMS114 [lung], at 0.21 μM for LOX-IMVI [melanoma], and at 0.23 μM for MKN74 [stomach]).

Figure optionsDownload as PowerPoint slide