Breast cancer in women is the second leading cause of cancer death and the most frequently diagnosed cancer among women worldwide. In 2014, according to the American Cancer Society, 232,670 new cases of invasive breast cancer and 62,570 of carcinoma in situ (CIS) were diagnosed. Multiple molecular targets have been identified for targeting breast cancer:  Estrogen, Progesterone and Human Epidermal Growth Factor 2 (HER2/neu) receptors. Luminal/estrogen positive (ER+) tumors are the most common type (60%-80%) of breast cancer. Targeting the estrogen receptor is a proven strategy used in the drug discovery process for developing treatments for human breast carcinoma. Cucurbitacin is one of the naturally occurring triterpenoid natural products that have been studied for their inhibitory activity against a variety of cancer cell lines. Nineteen structurally modified 3-methoxy steroidal analogs were synthesized by inserting functionalities at positions C-9, C-11, C-16 and C-17 of estrone that were deemed structurally significant sites on the Cucurbitacin skeleton. The biological activity of the synthesized compounds was evaluated using <i>in-vitro</i> ER binding assay, cell proliferation, cytotoxicity and anti-estrogenic assays using the MCF-7 cell line.  This was followed by further validation through conducting an in-silico molecular modeling study. The biological evaluation of these estrone analogs demonstrated that two steroidal analogs, among all estrone analogs examined, showed potent inhibition of cell growth up to 79-81% in a dose-dependent manner when stimulated by estradiol, suggesting that these compounds may have potential for treating breast cancer.<br/>

Design and biological screening of steroidal analogs as selective estrogen receptor modulators

249th National Meeting (2015)

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