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

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

Abstract

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.