Inhibition of tumor-associated human carbonic anhydrase isozymes IX and XII by a new class of substituted-phenylacetamido aromatic sulfonamides

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• 作者：Atilla Akdemir ; ?zlen G¨¹zel-Akdemir ; Andrea Scozzafava ; Clemente Capasso ; Claudiu T. Supuran
• 关键词：Carbonic anhydrases ; Cytosolic isoforms I and II ; Tumor-associated isoforms IX and XII ; Sulfonamides ; Docking
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：21
• 期：17
• 页码：5228-5232
• 全文大小：790 K

文摘

Here, we investigate 28 structurally new sulfonamides and their subsequent testing for enzyme inhibition of cytosolic and tumor-associated carbonic anhydrases (CAs, EC 4.2.1.1). The compounds showed very potent inhibition of four physiologically relevant human (h) CA isoforms, namely hCA I, II, IX and XII. Interestingly, the K_I values were in the nanomolar range for the tumor-associated hCA IX and hCA XII. Docking studies have revealed details regarding the very favorable interactions between the scaffolds of this new class of inhibitors and the active sites of the investigated CA isoforms. As there are reported cases of tumors overexpressing both CA II and IX, such potent inhibitors for the two isoforms as those detected in this work, may have applications for targeting more than one CA present in tumors.