一系列苯磺酰胺衍生物作为新型有效的碳酸酐酶IX和XII抑制剂。

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-02-01 Epub Date: 2025-01-29 DOI:10.1080/17568919.2025.2453420

Susanna Nencetti, Doretta Cuffaro, Lidia Ciccone, Alessio Nocentini, Miriana Di Stefano, Giulio Poli, Marco Macchia, Tiziano Tuccinardi, Elisa Nuti, Claudiu T Supuran, Armando Rossello, Elisabetta Orlandini

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引用次数: 0

摘要

目的：人体碳酸酐酶（hCAs）参与许多生理过程，包括呼吸、pH控制、离子运输、骨吸收和胃液分泌。最近，人们研究了CA IX和CA XII在癌症疾病中的作用，从而激发了这些同工异构体抑制剂的设计。材料和方法：在这里，我们使用尾部方法设计了一系列新的单芳基（1a-i）和双环（1j-n）苯磺酰胺衍生物CA IX和CA XII抑制剂。所有合成的化合物对一组hCAs进行了研究，大多数化合物对具有Ki值的CA II， CA IX和CA XII具有有效的CA抑制活性。结果与结论：最佳的CA抑制剂为Ki值在低纳摩尔范围内的1i （Ki = 9.4, 5.6和6.3 nM hCA II， IX和XII）。

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A series of benzensulfonamide derivatives as new potent carbonic anhydrase IX and XII inhibitors.

Aim: Human carbonic anhydrases (hCAs) are involved in many physiological processes including respiration, pH control, ion transport, bone resorption, and gastric fluid secretion. Recently, CA IX and CA XII have been studied for their role in cancer diseases, motivating the design of inhibitors of these isoforms.

Material and method: Here, we used the tail approach to design a new series of monoaryl (1a-i) and bicyclic (1j-n) benzensulfonamide derivatives CA IX and CA XII inhibitors. All synthesized compounds were investigated toward a panel of hCAs, and most of them exhibited potent CA inhibitory activity for CA II, CA IX and CA XII with K_i values. In silico studies were performed to investigate the binding mode between inhibitors and CA.

Results and conclusion: The best compound was 1i that showed a low nanomolar range of K_i value as CA inhibitor (K_i = 9.4, 5.6 and 6.3 nM hCA II, IX and XII, respectively).

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.