Photoinduced Evolution of Flavanones via C-C Bond Formation for Potent COMT Inhibition.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-07-02 DOI:10.1021/acs.jnatprod.5c00420

Xinyu Han, Pu Wang, Le Zhang, Jingchuan Lin, Zi-Qiong Zhou, Dong Lu, Ping Wang, Yu Zhang

引用次数: 0

Abstract

To explore and expand the chemical space of natural products, there is an urgent need for efficient and functional modification of natural products. Here, a photoinduced strategy is reported to access flavanone-based pseudonatural products via late-stage functionalization. This mild procedure enables the chemical evolution of diverse flavanones via introduction of 1,1-diarylalkane scaffolds. The method features mild reaction conditions, operational simplicity, high functional group tolerance, and scalability. Moreover, the cheminformatics results indicate that the pseudonatural products possess excellent drug-like properties and shape diversity. Finally, the catechol-O-methyltransferase (COMT) inhibitory activity analysis demonstrated that compounds 26d and 28d exhibit potent COMT inhibition, with IC₅₀ values of 85.2 and 99.7 nM, respectively, providing valuable insights for the development of novel flavanone-based non-nitrocatechol COMT inhibitors for Parkinson's disease treatment.

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通过C-C键形成的光诱导黄酮类化合物的进化对COMT的有效抑制。

为了探索和拓展天然产物的化学空间，迫切需要对天然产物进行高效的功能性修饰。本文报道了一种光诱导策略，通过后期功能化获得基于黄酮的伪天然产物。这个温和的过程通过引入1,1-二芳烷支架，使各种黄酮的化学进化成为可能。该方法反应条件温和，操作简单，官能团容忍度高，具有可扩展性。此外，化学信息学结果表明，伪天然产物具有优异的类药物性质和形状多样性。最后，儿茶酚- o -甲基转移酶（COMT）抑制活性分析表明，化合物26d和28d表现出有效的COMT抑制作用，IC50值分别为85.2和99.7 nM，为开发新型黄酮基非硝基儿茶酚COMT抑制剂治疗帕金森病提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.