Selenium analogues of rintodestrant (G1T48) as potent estrogen receptor modulators and downregulators?

New Journal of Chemistry Pub Date: 2023-07-25 DOI: 10.1039/D3NJ01739G

Abstract

Targeted therapy is one of the modern directions in the fight against cancer. Nowadays, selective estrogen receptor modulators (SERMs) and downregulators (SERDs) are used as the first-line medical treatment for estrogen receptor positive (ER+) tumors. Herein we report the design and synthesis of 7 novel benzoselenophenes, and their ER-α binding activity and cytotoxicity. The TR-FRET competitive ER-α binding experiments have shown that (E)-3-(4-((6-hydroxy-2-(4-hydroxybenzoyl)benzo[b]selenophen-3-yl)oxy)phenyl)acrylic acid (21b) is a considerably more effective ER-α binder (IC50 = 0.44 nM) than the widely known SERM drug raloxifene (IC50 = 1.78 nM). Furthermore, 21b and other obtained selenium analogues are not toxic in rat cardiomyoblasts (H9C2), indicating that the substituted benzo[b]selenophene is a prospective scaffold for the development of ER-α modulators and downregulators for the treatment of ER+ cancers.

Graphical abstract: Selenium analogues of rintodestrant (G1T48) as potent estrogen receptor modulators and downregulators
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