Lasamide, a Potent Human Carbonic Anhydrase Inhibitor from the Market: Inhibition Profiling and Crystallographic Studies

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2024-09-30 DOI:10.1021/acsmedchemlett.4c0034110.1021/acsmedchemlett.4c00341

Chiara Baroni, Ilaria D’Agostino, Gioele Renzi, Jaydeo T. Kilbile, Yasinalli Tamboli, Marta Ferraroni*, Simone Carradori, Clemente Capasso, Fabrizio Carta* and Claudiu T. Supuran,

引用次数: 0

Abstract

Lasamide is a synthetic precursor and a contaminant of the diuretic Furosemide manufacturing process and represents a highly valuable building block for fragment-based drug discovery approaches. We assessed the ability of Lasamide to inhibit in vitro the human-expressed Carbonic Anhydrases by means of the stopped-flow technique, and we assessed its binding modes within hCAs II and XII-mimic catalytic clefts by X-ray crystallography. Interestingly, an unprecedented crystal form for the hCA IX mimic H-tag is reported and discussed herein.

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Lasamide 是一种来自市场的强效人类碳酸酐酶抑制剂：抑制谱分析和晶体学研究

拉扎米酰胺是一种合成前体，也是利尿剂呋塞米生产过程中的一种污染物，是基于片段的药物发现方法中极具价值的构件。我们通过停流技术评估了 Lasamide 在体外抑制人类表达的碳酸酐酶的能力，并通过 X 射线晶体学评估了它在 hCAs II 和 XII 模拟催化裂隙中的结合模式。有趣的是，本文报告并讨论了一种前所未有的 hCA IX 模拟 H 标记的晶体形式。

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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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.