Toward Resolving the Resveratrol Conundrum: Synthesis and in Vivo Pharmacokinetic Evaluation of BCP-Resveratrol
Toward Resolving the Resveratrol Conundrum: Synthesis and in Vivo Pharmacokinetic Evaluation of BCP-Resveratrol
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DOI：
10.1021/acsmedchemlett.7b00018
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发表时间：
2017-05-01
影响因子：
4.2
通讯作者：
Adsool, Vikrant A.
中科院分区：
文献类型：
--
作者：
Goh, Yi Ling;Cui, Yan Ting;Adsool, Vikrant A.
在过去的几十年里，白藜芦醇由于其令人印象深刻的生物活性而获得了重要性;然而，其作为药物的真正潜力受到其生物利用度差的严重限制。事实上，一些研究表明这种生物利用度特性是白藜芦醇潜在临床应用的主要障碍。为了减轻这种药代动力学问题，我们设想了白藜芦醇到双环[1.1.1]-戊烷（BCP）白藜芦醇的战术生物电子等排修饰。依赖于BCP-支架所展示的有益的生物电子等排潜力，我们假设BCP白藜芦醇与其天然对应物相比具有固有的更好的体内PK特征。为了验证这样的假设，有必要确保合成这种新结构。在此，我们描述了BCP-白藜芦醇的首次合成，并公开了其PK性质。
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 roadblock 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.