Synthesis of Tamoxifen-Artemisinin and Estrogen-Artemisinin Hybrids Highly Potent Against Breast and Prostate Cancer

In the search for new and effective treatments of breast and prostate cancer, a series of hybrid compounds based on tamoxifen, estrogens, and artemisinin were successfully synthesized and analyzed for theirin vitroactivities against human prostate (PC-3) and breast cancer (MCF-7) cell lines. Most of the hybrid compounds exhibit a strong anticancer activity against both cancer cell lines - for example, EC50(PC-3) down to 1.07 mu M, and EC50(MCF-7) down to 2.08 mu M - thus showing higher activities than their parent compounds 4-hydroxytamoxifen (afimoxifene,7; EC50=75.1 (PC-3) and 19.3 mu M (MCF-7)), dihydroartemisinin (2; EC50=263.6 (PC-3) and 49.3 mu M (MCF-7)), and artesunic acid (3; EC50=195.1 (PC-3) and 32.0 mu M (MCF-7)). The most potent compounds were the estrogen-artemisinin hybrids27and28(EC50=1.18 and 1.07 mu M, respectively) against prostate cancer, and hybrid23(EC50=2.08 mu M) against breast cancer. These findings demonstrate the high potential of hybridization of artemisinin and estrogens to further improve their anticancer activities and to produce synergistic effects between linked pharmacophores.