Chiara Baroni, Ilaria D’Agostino, Gioele Renzi, Jaydeo T. Kilbile, Yasinalli Tamboli, Marta Ferraroni*, Simone Carradori, Clemente Capasso, Fabrizio Carta* and Claudiu T. Supuran,
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引用次数: 0
摘要
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。
Lasamide, a Potent Human Carbonic Anhydrase Inhibitor from the Market: Inhibition Profiling and Crystallographic Studies
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.
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.
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