Steroidal N-Sulfonylimidates: Synthesis and biological evaluation in breast cancer cells

Unique derivatives of androstene and estrane series containing N-sulfonylimidate pendants were pre- pared from 17 alpha-ethynyl steroids via Cu-catalyzed azide-alkyne cycloaddition to tosyl azide in the presence of alcohols. The synthesized compounds were screened for cytotoxicity against human breast cancer cell lines and ER alpha agonist activity. The hit compound 3,17 beta-dimethoxy-17 alpha-[iso-propyl-2'-N- tosylacetimidatejestra-1,3,5((10))-triene (4n) had no ER alpha-mediated hormonal activity and was found to exhibit potent cytotoxic effect in an ER alpha-positive breast cancer cell line. N-Sulfonylimidate 4n displayed high antiproliferative potency against triple-negative MDA-MB-231 breast cancer cells, while it was non-toxic towards normal mammary epithelial cells. Compound 4n was found to alter activity of various signaling pathways (NF-kappa B, Slug, cyclin D1, ERK) supporting the growth and invasiveness of tumor cells. (C) 2019 Elsevier Masson SAS. All rights reserved.