Affinity for Estrogen Receptor α (ERα) in a <i>trans</i>-Stilbene Derivative Containing a Pyridoxine Fragment-Reference-Cited by-同舟云学术

Affinity for Estrogen Receptor α (ERα) in a <i>trans</i>-Stilbene Derivative Containing a Pyridoxine Fragment

Published:2024-07-08 Issue:2 Volume:166 Page:255-265
ISSN:2500-218X
Container-title:Uchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki
language:
Short-container-title:jour

Author:

Bondar O. V.¹,Karut R.¹,Mostovaya O. A.¹,Pugachev M. V.¹,Iksanova A. G.¹,Shtyrlin Yu. G.¹

Affiliation:

1. Kazan Federal University

Abstract

Molecular targets for a promising antitumor agent based on trans-stilbene containing a pyridoxine fragment were identified. The lead compound, (E)-6-(3,4-dimethoxystyryl)-2,2,5,8-tetramethyl-4H-[1,3] dioxino[4,5-c]pyridine, was found to selectively induce apoptosis in MCF-7 breast adenocarcinoma cells overexpressing estrogen receptor, but not in MDA-MB-231 cells negative for estrogen receptor. The mechanism by which the novel trans-stilbene derivative acts as a selective estrogen receptor modulator was analyzed, and the affinity for human estrogen receptor α (ERα) was assessed by fluorescence polarization. Unlike its structural analogs—tamoxifen and raloxifene, the lead compound showed no affinity for ERα and did not form complexes with it. Therefore, it was concluded that the selective action of the pyridoxine-containing derivative of trans-stilbene on estrogen-positive breast cancer cells occurs through an alternative mechanism. The EC 50 values for the displacement of the fluorescent ligand from the ERα active site were 22, 120, and 595 nM for estradiol, raloxifene, and tamoxifen, respectively.

Publisher

Kazan Federal University

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