Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol

In this study, we synthesized and evaluated silanol-based bisphenol derivatives as stable isosteres of bis(4-hydroxyphenyl)methanol. The developed silanols exhibited estrogen receptor (ER)-modulating activity. Among them, bis(4-hydroxyphenyl)(methyl)silanol (5a) showed a characteristic ER subtype se...

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Detalles Bibliográficos
Autores principales: Matsumoto, Yuichiro, Hashimoto, Yuichi, Fujii, Shinya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496907/
https://www.ncbi.nlm.nih.gov/pubmed/37705989
http://dx.doi.org/10.1039/d3ra04656g
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author Matsumoto, Yuichiro
Hashimoto, Yuichi
Fujii, Shinya
author_facet Matsumoto, Yuichiro
Hashimoto, Yuichi
Fujii, Shinya
author_sort Matsumoto, Yuichiro
collection PubMed
description In this study, we synthesized and evaluated silanol-based bisphenol derivatives as stable isosteres of bis(4-hydroxyphenyl)methanol. The developed silanols exhibited estrogen receptor (ER)-modulating activity. Among them, bis(4-hydroxyphenyl)(methyl)silanol (5a) showed a characteristic ER subtype selectivity, namely, antagonistic activity toward ERα and agonistic activity toward ERβ. Docking simulation indicated that the silanol moiety plays a key role in this selectivity. Our results suggest that silanol-based bisphenols offer a unique scaffold for biologically active compounds.
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spelling pubmed-104969072023-09-13 Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol Matsumoto, Yuichiro Hashimoto, Yuichi Fujii, Shinya RSC Adv Chemistry In this study, we synthesized and evaluated silanol-based bisphenol derivatives as stable isosteres of bis(4-hydroxyphenyl)methanol. The developed silanols exhibited estrogen receptor (ER)-modulating activity. Among them, bis(4-hydroxyphenyl)(methyl)silanol (5a) showed a characteristic ER subtype selectivity, namely, antagonistic activity toward ERα and agonistic activity toward ERβ. Docking simulation indicated that the silanol moiety plays a key role in this selectivity. Our results suggest that silanol-based bisphenols offer a unique scaffold for biologically active compounds. The Royal Society of Chemistry 2023-09-12 /pmc/articles/PMC10496907/ /pubmed/37705989 http://dx.doi.org/10.1039/d3ra04656g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Matsumoto, Yuichiro
Hashimoto, Yuichi
Fujii, Shinya
Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol
title Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol
title_full Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol
title_fullStr Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol
title_full_unstemmed Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol
title_short Development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol
title_sort development of subtype-selective estrogen receptor modulators using the bis(4-hydroxyphenyl)silanol core as a stable isostere of bis(4-hydroxyphenyl)methanol
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496907/
https://www.ncbi.nlm.nih.gov/pubmed/37705989
http://dx.doi.org/10.1039/d3ra04656g
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AT hashimotoyuichi developmentofsubtypeselectiveestrogenreceptormodulatorsusingthebis4hydroxyphenylsilanolcoreasastableisostereofbis4hydroxyphenylmethanol
AT fujiishinya developmentofsubtypeselectiveestrogenreceptormodulatorsusingthebis4hydroxyphenylsilanolcoreasastableisostereofbis4hydroxyphenylmethanol

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