Toward Resolving the Resveratrol Conundrum: Synthesis and in Vivo Pharmacokinetic Evaluation of BCP-Resveratrol

ACS Medicinal Chemistry Letters
Yi Ling GohVikrant A Adsool

Abstract

Over the last few decades, resveratrol has gained significance due to its impressive array of biological activities; however, its true potential as a drug has been severely constrained by its poor bioavailability. Indeed, several studies have implicated this bioavailability trait as a major road-block to resveratrol's potential clinical applications. To mitigate this pharmacokinetic issue, we envisioned a tactical bioisosteric modification of resveratrol to bicyclo[1.1.1]pentane (BCP) resveratrol. Relying on the beneficial bioisosteric potential demonstrated by the BCP-scaffold, we hypothesized that BCP-resveratrol would have an inherently better in vivo PK profile as compared to its natural counterpart. To validate such a hypothesis, it was necessary to secure a synthetic access to this novel structure. Herein we describe the first synthesis of BCP-resveratrol and disclose its PK properties.

References

Jul 20, 2002·Free Radical Biology & Medicine·Miguel AsensiJose M Estrela
Aug 31, 2006·Journal of the American Chemical Society·Jérôme WaserErick M Carreira
Feb 24, 2007·European Journal of Medicinal Chemistry·W Zhang, M L Go
Dec 1, 2010·Cancer Chemotherapy and Pharmacology·Izet M KapetanovicDavid L McCormick
Mar 19, 2011·Journal of Medicinal Chemistry·Nicholas A Meanwell
Feb 7, 2014·Endocrine-related Cancer·Lindsay G CarterKevin J Pearson
Mar 19, 2014·Organic Letters·Yi Ling GohVikrant A Adsool
Oct 28, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·James M Smoliga, Otis Blanchard
Jan 22, 2015·Chemical Communications : Chem Comm·Navanita T ThirumoorthiVikrant A Adsool
Apr 4, 2015·Chemical Reviews·Mitchell H KeylorCorey R J Stephenson
Sep 24, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qing LiuMi Kyeong Lee
Nov 11, 2015·Organic & Biomolecular Chemistry·Yi Ling Goh, Vikrant A Adsool

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Citations

Jan 24, 2019·Organic & Biomolecular Chemistry·Pavel K Mykhailiuk
Oct 7, 2018·Angewandte Chemie·Russell A Shelp, Patrick J Walsh
Jul 11, 2019·Angewandte Chemie·Nisalak TrongsiriwatPatrick J Walsh
Nov 23, 2019·Journal of the Science of Food and Agriculture·Bingren Tian, Jiayue Liu
Nov 8, 2019·Chemistry : a European Journal·Nitika GroverMathias O Senge
Jul 13, 2018·Chemical Science·Dimitri F J CaputoEdward A Anderson
Mar 14, 2021·Nature Communications·Marie L J WongEdward A Anderson
May 4, 2021·RSC Medicinal Chemistry·Matthias R BauerBenjamin C Whitehurst
May 27, 2021·Chemical Communications : Chem Comm·Zhen WuChen Zhu
Jun 25, 2021·The Journal of Organic Chemistry·Vasyl RipenkoPavel K Mykhailiuk
Apr 13, 2020·Chemical Science·Alistair J SterlingFernanda Duarte
Jun 22, 2021·Angewandte Chemie·Joseph M AndersonDarren L Poole
Mar 15, 2019·Organic Letters·Marie L J WongEdward A Anderson
Aug 15, 2018·Chemical Research in Toxicology·Liang-Liang Bao, Zai-Qun Liu
Sep 26, 2019·The Journal of Organic Chemistry·Roman M BychekPavel K Mykhailiuk
Aug 18, 2020·Journal of Medicinal Chemistry·Tanaji T Talele
Oct 1, 2021·Journal of Medicinal Chemistry·Murugaiah A M Subbaiah, Nicholas A Meanwell

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