Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents

作者：Alsayari Abdulrhman; Kopel Lucas; Ahmed Mahmoud Salama; Pay Adam; Carlson Taylor; Halaweish Fathi T^*

来源：Steroids, 2017, 118: 32-40.

DOI：10.1016/j.steroids.2016.11.005

• Breast cancer
• Estrone
• Estrogenic/anti-estrogenic activity
• Breast cancer (MCF-7) cell lines

Series of estrone based analogs were synthetically investigated at positions C-9, C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7 and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This was further validated by Estrogen Receptor-alpha (ER-alpha) and Estrogen Receptor-alpha (ER-alpha) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-a at 5.49 mu M, while LA-10 did not show any binding affinity towards neither ER-alpha nor ER-beta; suggesting another mechanism for inhibition. This was validated by in silico molecular docking simulations of LA-7 to reveal the optimum binding affinity of LA-7 towards ER-alpha.

• 出版日期2017-2