四唑是一种抑制碳酸酐酶的新型锌结合剂化学型。

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2024-12-25 eCollection Date: 2025-01-09 DOI:10.1021/acsmedchemlett.4c00562

Simone Giovannuzzi, Andrea Angeli, Paloma Begines, Marta Ferraroni, Alessio Nocentini, Claudiu T Supuran

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引用次数: 0

摘要

本文提出了四唑基团作为锌结合战斗部，用于抑制金属酶碳酸酐酶。一组含有四氮唑片段的合成衍生物被评估为人类同种异构体的抑制剂，其K I值在亚微摩尔和低至中微摩尔范围（0.62-19.6 μM）之间。进行了x射线晶体学研究，以深入了解它们与靶酶的结合模式。这些发现标志着在寻找除经典磺胺类药物以外的抑制性化学型方面取得了重大进展。

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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Tetrazole Is a Novel Zinc Binder Chemotype for Carbonic Anhydrase Inhibition.

The tetrazole group is here proposed as a zinc-binding warhead for the inhibition of the metalloenzyme carbonic anhydrases. A set of synthesized derivatives incorporating the tetrazole moiety were evaluated as inhibitors against a panel of human isoforms, exhibiting K _I values spanning between the submicromolar and low-to-medium micromolar ranges (0.62-19.6 μM). X-ray crystallographic studies were conducted to gain insights into their modes of binding to the target enzyme. These findings mark a significant advancement in the search for inhibitory chemotypes other than classical sulfonamides.

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.