Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines

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• 作者：Nagwa M. Abdel Gawad^a ; Noha H. Amin^b ; ^{hani.noha@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Mohammed T. Elsaadi^b ; Fatma M.M. Mohamed^b ; Andrea Angeli^c ; Viviana De Luca^d ; Clemente Capasso^d ; Claudiu T. Supuran^c ; ^{claudiu.supuran@unifi.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Carbonic anhydrase ; Inhibitor ; Sulfonamide ; Antitumor ; Cytotoxic agent
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：24
• 期：13
• 页码：3043-3051
• 全文大小：826 K

文摘

A series of 4-(thiazol-2-ylamino)-benzenesulfonamides was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory and cytotoxic activity on human breast cancer cell line MCF-7. Human (h) CA isoforms I, II and IX were included in the study. The new sulfonamides showed excellent inhibition of all three isoforms, with K_Is in the range of 0.84–702 nM against hCA I, of 0.41–288 nM against hCA II and of 5.6–29.2 against the tumor-associated hCA IX, a validated anti-tumor target, with a sulfonamide (SLC-0111) in Phase I clinical trials for the treatment of hypoxic, metastatic solid tumors overexpressing CA IX. The new compounds showed micromolar inhibition of growth efficacy against breast cancer MCF-7 cell lines.