title: Design, synthesis, and biological evaluation of steroidal analogs as estrogenic/anti-estrogenic agents.
abstract: 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.
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
authors.forename: Abdulrhman
authors.initials: A
authors.lastname: Alsayari
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University, Box 2202, Brookings, SD 57007, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Kopel
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, Al-Sherouk City, Cairo, Egypt.
authors.forename: Mahmoud Salama
authors.initials: MS
authors.lastname: Ahmed
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University, Box 2202, Brookings, SD 57007, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Pay
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University, Box 2202, Brookings, SD 57007, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Carlson
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University, Box 2202, Brookings, SD 57007, USA. Electronic address: fathi.halaweish@sdstate.edu.
authors.forename: Fathi T
authors.initials: FT
authors.lastname: Halaweish
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D004970:Estrone
keywords: Breast cancer; Breast cancer (MCF-7) cell lines; Estrogenic/anti-estrogenic activity; Estrone