一系列作为新型高效碳酸酐酶IX和XII抑制剂的苯磺酰胺衍生物。
A series of benzensulfonamide derivatives as new potent carbonic anhydrase IX and XII inhibitors.
作者信息
Nencetti Susanna, Cuffaro Doretta, Ciccone Lidia, Nocentini Alessio, Di Stefano Miriana, Poli Giulio, Macchia Marco, Tuccinardi Tiziano, Nuti Elisa, Supuran Claudiu T, Rossello Armando, Orlandini Elisabetta
机构信息
Department of Pharmacy, University of Pisa, Pisa, Italy.
Department of Neurofarba, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Sesto Fiorentino, Italy.
出版信息
Future Med Chem. 2025 Feb;17(3):271-285. doi: 10.1080/17568919.2025.2453420. Epub 2025 Jan 29.
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 () and bicyclic () 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 values. studies were performed to investigate the binding mode between inhibitors and CA.
RESULTS AND CONCLUSION
The best compound was that showed a low nanomolar range of K value as CA inhibitor (K = 9.4, 5.6 and 6.3 nM hCA II, IX and XII, respectively).
目的
人类碳酸酐酶（hCAs）参与许多生理过程，包括呼吸、pH调节、离子转运、骨吸收和胃液分泌。最近，CA IX和CA XII在癌症疾病中的作用得到了研究，这推动了这些同工型抑制剂的设计。
材料与方法
在此，我们采用尾部方法设计了一系列新的单芳基（）和双环（）苯磺酰胺衍生物作为CA IX和CA XII抑制剂。所有合成的化合物都针对一组hCAs进行了研究，其中大多数对CA II、CA IX和CA XII表现出强效的CA抑制活性，其K值各异。进行了研究以探究抑制剂与CA之间的结合模式。
结果与结论
最佳化合物是，作为CA抑制剂，其K值处于低纳摩尔范围（分别为hCA II、IX和XII的K = 9.4、5.6和6.3 nM）。
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