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

- Series of estrone analogs were synthesized.
- Cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activities were evaluated.
- LA-7 alcohol derivative exhibited selective anti-estrogenic activity towards ER-α at 5.49 μM.

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 5.49 μM, 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.

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