3-Halo-3-nitro-aza/thioflavanones：在hDNMT3A催化口袋中具有双位点结合模式的DNMT抑制剂。

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-11-28 DOI:10.1016/j.bmc.2024.117988

Alexandra Serhouni, Francesco Calzaferri, Yannick Bessina, Arie van der Lee, Paola B Arimondo, Maxime Louet, Jean-Yves Winum, Marie Lopez

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引用次数: 0

摘要

类黄酮衍生物是天然产物类似物，作为DNA甲基化调节剂在治疗应用中表现出极大的兴趣。在本文中，我们报道了新的合成途径，以获得10种新的类黄酮衍生物（即3-卤-3-硝基-aza/硫代黄酮），作为潜在的DNA甲基转移酶抑制剂。在我们的体外荧光检测中，这些化合物对人DNA甲基转移酶3A具有微摩尔抑制作用。重要的是，对酶口袋中该系列代表性化合物的对接研究突出了hDNMT3A催化口袋中从未描述过的相互作用模式。

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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3-Halo-3-nitro-aza/thioflavanones: DNMT inhibitors with a two-site binding mode in the hDNMT3A catalytic pocket.

Flavonoid derivatives are natural product analogues that have shown great interest for therapeutic applications as modulators of DNA methylation. In this article we report new synthesis pathways to access ten novel flavonoid derivatives (i.e. 3-halo-3-nitro-aza/thioflavanones) to be used as potential DNA methyltransferase inhibitors. These compounds have a micromolar inhibition against human DNA methyltransferase 3A in our in vitro fluorescence-based assay. Importantly, a docking study of representative compounds of this series in the enzyme pocket highlights a mode of interaction in the catalytic pocket of hDNMT3A that has never been described.

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.