Cargando…

Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models

Silibinin, also known as silybin, is isolated from milk thistle (Silybum marianum). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeut...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Sitong, Chen, Guanglin, Chen, Eva Y., Farshidpour, Leyla S., Zhang, Qiang, Wang, Guangdi, Chen, Qiao-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145751/
https://www.ncbi.nlm.nih.gov/pubmed/37111288
http://dx.doi.org/10.3390/ph16040531
_version_ 1785034411954143232
author Wu, Sitong
Chen, Guanglin
Chen, Eva Y.
Farshidpour, Leyla S.
Zhang, Qiang
Wang, Guangdi
Chen, Qiao-Hong
author_facet Wu, Sitong
Chen, Guanglin
Chen, Eva Y.
Farshidpour, Leyla S.
Zhang, Qiang
Wang, Guangdi
Chen, Qiao-Hong
author_sort Wu, Sitong
collection PubMed
description Silibinin, also known as silybin, is isolated from milk thistle (Silybum marianum). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use. Our research group has been working on optimizing silibinin for the potential treatment of castration-resistant prostate cancer. Our previous studies established 5,7,20-O-trimethylsilybins as promising lead compounds as they can selectively suppress androgen receptor (AR)-positive LNCaP cell proliferation. Encouraged by the promising data, the present study aims to investigate the relationships between the core structure of 5,7,20-O-trimethylsilybin and their antiproliferative activities towards AR-positive (LNCaP) and AR-negative prostate cancer cell lines (PC-3 and DU145). The structure–activity relationships among the four different core structures (including flavanonol-type flavonolignan (silibinin), flavone-type flavonolignan (hydnocarpin D), chalcone-type flavonolignan, and taxifolin (a flavonolignan precursor) indicate that 5,7,20-O-trimethylsilybins are the most promising scaffold to selectively suppress AR-positive LNCaP prostate cancer cell proliferation. Further investigation on the antiproliferative potency of their optically enriched versions of the most promising 5,7,20-O-trimethylsilybins led to the conclusion that (10R,11R) derivatives (silybin A series) are more potent than (10S,11S) derivatives (silybin B series) in suppressing AR positive LNCaP cell proliferation.
format Online
Article
Text
id pubmed-10145751
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-101457512023-04-29 Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models Wu, Sitong Chen, Guanglin Chen, Eva Y. Farshidpour, Leyla S. Zhang, Qiang Wang, Guangdi Chen, Qiao-Hong Pharmaceuticals (Basel) Article Silibinin, also known as silybin, is isolated from milk thistle (Silybum marianum). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use. Our research group has been working on optimizing silibinin for the potential treatment of castration-resistant prostate cancer. Our previous studies established 5,7,20-O-trimethylsilybins as promising lead compounds as they can selectively suppress androgen receptor (AR)-positive LNCaP cell proliferation. Encouraged by the promising data, the present study aims to investigate the relationships between the core structure of 5,7,20-O-trimethylsilybin and their antiproliferative activities towards AR-positive (LNCaP) and AR-negative prostate cancer cell lines (PC-3 and DU145). The structure–activity relationships among the four different core structures (including flavanonol-type flavonolignan (silibinin), flavone-type flavonolignan (hydnocarpin D), chalcone-type flavonolignan, and taxifolin (a flavonolignan precursor) indicate that 5,7,20-O-trimethylsilybins are the most promising scaffold to selectively suppress AR-positive LNCaP prostate cancer cell proliferation. Further investigation on the antiproliferative potency of their optically enriched versions of the most promising 5,7,20-O-trimethylsilybins led to the conclusion that (10R,11R) derivatives (silybin A series) are more potent than (10S,11S) derivatives (silybin B series) in suppressing AR positive LNCaP cell proliferation. MDPI 2023-04-02 /pmc/articles/PMC10145751/ /pubmed/37111288 http://dx.doi.org/10.3390/ph16040531 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Sitong
Chen, Guanglin
Chen, Eva Y.
Farshidpour, Leyla S.
Zhang, Qiang
Wang, Guangdi
Chen, Qiao-Hong
Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models
title Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models
title_full Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models
title_fullStr Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models
title_full_unstemmed Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models
title_short Core Structure–Activity Relationship Studies of 5,7,20-O-Trimethylsilybins in Prostate Cancer Cell Models
title_sort core structure–activity relationship studies of 5,7,20-o-trimethylsilybins in prostate cancer cell models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145751/
https://www.ncbi.nlm.nih.gov/pubmed/37111288
http://dx.doi.org/10.3390/ph16040531
work_keys_str_mv AT wusitong corestructureactivityrelationshipstudiesof5720otrimethylsilybinsinprostatecancercellmodels
AT chenguanglin corestructureactivityrelationshipstudiesof5720otrimethylsilybinsinprostatecancercellmodels
AT chenevay corestructureactivityrelationshipstudiesof5720otrimethylsilybinsinprostatecancercellmodels
AT farshidpourleylas corestructureactivityrelationshipstudiesof5720otrimethylsilybinsinprostatecancercellmodels
AT zhangqiang corestructureactivityrelationshipstudiesof5720otrimethylsilybinsinprostatecancercellmodels
AT wangguangdi corestructureactivityrelationshipstudiesof5720otrimethylsilybinsinprostatecancercellmodels
AT chenqiaohong corestructureactivityrelationshipstudiesof5720otrimethylsilybinsinprostatecancercellmodels