Synthesis and biological evaluation of aminoalkyloxy derivatives of 1,3,5,(10) estratriene-like steroids as potential anti-breast cancer agents Free

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Breast cancer is second only to cardiovascular disease in causing death in women between the ages of 35 and 55 years. It is also the second most common cause of death in women older than 55 years of age. Estrogens are important hormones in the female body. These steroids interact with multiple organ systems and make major impacts on the physiological events that occur throughout the female’s life. Among the estrogens, estradiol is the most potent because of its high binding affinity for the estrogen receptors. Tamoxifen, a therapeutically and clinically available selective estrogen receptor modulator(SERM) has been shown to be effective in the treatment of breast cancer. Nevertheless, tamoxifen have been associated with endometrial cancer due to its estrogenic activity within the uterus. Several chemically unrelated compounds have been found to demonstrate activities similar to that of SERMs through interaction with estrogen receptors. We have synthesized compounds by combining a portion of the chemical features of tamoxifen, the aminoalkyloxy functional group, with the rigid structure of estradiol and compare the activity. Throughmodifying the 3-OH position on the Estradiol A-ring with different aminoalkyloxy derivatives; and opening the D-ring at the 17th position the synthesis of these compounds have been achieved. Receptor binding assays and gene proliferation studies have been evaluated using MCF-7 cells, in vitro, to evaluate their effectiveness in treatment of breast cancer.In synthesizing these specific types of compounds, it is hypothesized that they will have activity equal to or better than that of 4-hydroxytamoxifen, the active metabolite of Tamoxifen. Therefore, these compounds could be of use in the market for effectively treating patients affected by breast cancer.