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

In 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 towards their in vitro activities against human prostate (PC-3) and breast cancer (MCF-7) cell lines. Most of the hybrid compounds exhibit a strong anti-cancer activity against both cancer cell lines e.g., EC 50 (PC-3) down to 1.07 µM and EC 50 (MCF-7) down to 2.08 µM, thus showing higher activities than their parent compounds 4-hydroxytamoxifen (Afimoxifene, 7 ) (EC 50 (PC-3) = 75.1 µM and EC 50 (MCF-7) = 19.3 µM), dihydroartemisinin ( 2 ) (EC 50 (PC-3) = 263.6 µM and EC 50 (MCF-7) = 49.3 µM) and artesunic acid ( 3 ) (EC 50 (PC-3) = 195.1 µM and EC 50 (MCF-7) = 32.0 µM). The most potent compounds were the estrogen-artemisinin hybrids 27 and 28 (EC 50 (PC-3) = 1.18 µM and 1.07 µM, correspondingly) against prostate cancer and hybrid 23 (EC 50 (MCF-7) = 2.08 µM) 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.