Alsayari Abdulrhman, Kopel Lucas, Ahmed Mahmoud Salama, Pay Adam, Carlson Taylor, Halaweish Fathi T
Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
Department of Chemistry and Biochemistry, South Dakota State University, Box 2202, Brookings, SD 57007, USA.
Steroids. 2017 Feb;118:32-40. doi: 10.1016/j.steroids.2016.11.005. Epub 2016 Nov 20.
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-α (ER-α) and Estrogen Receptor-β (ER-β) competitive binding assays to reveal the high selective affinity of LA-7 towards ER-α at 5.49μM, while LA-10 did not show any binding affinity towards neither ER-α nor ER-β; 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-α.
对一系列基于雌酮的类似物在C-9、C-11、C-16和C-17位进行了合成研究，通过评估细胞增殖、细胞毒性和雌激素/抗雌激素活性进行生物学评价。LA-7和LA-10显示出具有抑制雌激素特性的潜力。雌激素受体-α（ER-α）和雌激素受体-β（ER-β）竞争性结合试验进一步证实了这一点，该试验显示LA-7在5.49μM时对ER-α具有高选择性亲和力，而LA-10对ER-α和ER-β均未显示任何结合亲和力；这表明存在另一种抑制机制。通过LA-7的计算机分子对接模拟验证了这一点，以揭示LA-7对ER-α的最佳结合亲和力。
