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

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

Journal

European Journal of Medicinal Chemistry
ISSN: 1768-3254 , E-ISSN: 0223-5234

Output data

Year: 2019, Volume: 179, Pages: 694-706 Pages count : 13 DOI: 10.1016/j.ejmech.2019.06.048

Authors

Volkova Yulia A. ¹ , Kozlov Andrey S. ¹ , Kolokolova Marya K. ¹ , Uvarov Denis Y. ¹ , Gorbatov Sergey A. ¹ , Andreeva Olga E. ² , Scherbakov Alexander M. ² , Zavarzin Igor V. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp, 119991, Moscow, Russia
2	Department of Experimental Tumor Biology, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, 24 Kashirskoye sh, Moscow, 115522, Russia

Unique derivatives of androstene and estrane series containing N-sulfonylimidate pendants were prepared from 17α-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 ERα agonist activity. The hit compound 3,17β-dimethoxy-17α-[iso-propyl-2′-N-tosylacetimidate]estra-1,3,5(10)-triene (4n) had no ERα-mediated hormonal activity and was found to exhibit potent cytotoxic effect in an ERα-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-κB, Slug, cyclin D1, ERK) supporting the growth and invasiveness of tumor cells.

Volkova Y.A. , Kozlov A.S. , Kolokolova M.K. , Uvarov D.Y. , Gorbatov S.A. , Andreeva O.E. , Scherbakov A.M. , Zavarzin I.V.
Steroidal N-Sulfonylimidates: Synthesis and biological evaluation in breast cancer cells
European Journal of Medicinal Chemistry. 2019. V.179. P.694-706. DOI: 10.1016/j.ejmech.2019.06.048 WOS Scopus OpenAlex

≡ Web of science:	WOS:000486133100051
≡ Scopus:	2-s2.0-85068421421
≡ OpenAlex:	W2952714715