Pursuing on our efforts toward searching for efficient hCA IX and hCA XII inhibitors, herein we report the design and synthesis of new sets of benzofuran-based sulphonamides (4a,b, 5a,b, 9a-c, and 10a-d), featuring the zinc anchoring benzenesulfonamide moiety linked to a benzofuran tail via a hydrazine or hydrazide linker. All the target benzofurans were examined for their inhibitory activities toward isoforms hCA I, II, IX, and XII. The target tumour-associated hCA IX and XII isoforms were efficiently inhibited with KIs spanning in ranges 10.0-97.5 and 10.1-71.8 nM, respectively. Interestingly, arylsulfonehydrazones 9 displayed the best selectivity toward hCA IX and XII over hCA I (SIs: 39.4-250.3 and 26.0-149.9, respectively), and over hCA II (SIs: 19.6-57.1 and 13.0-34.2, respectively). Furthermore, the target benzofurans were assessed for their anti-proliferative activity, according to US-NCI protocol, toward a panel of sixty cancer cell lines. Only benzofurans 5b and 10b possessed selective and moderate growth inhibitory activity toward certain cancer cell lines.

中文翻译：

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新型基于苯并呋喃的磺酰胺类作为选择性碳酸酐酶IX和XII抑制剂：合成和体外生物学评估。

在我们努力寻找有效的hCA IX和hCA XII抑制剂的基础上，我们在此报告了新的基于苯并呋喃的磺酰胺类化合物（4a，b，5a，b，9a-c和10a-d）的设计和合成。通过肼或酰肼连接基连接至苯并呋喃尾的锌锚定苯磺酰胺部分。检查所有目标苯并呋喃对hCA I，II，IX和XII亚型的抑制活性。与靶肿瘤相关的hCA IX和XII同工型分别被KIs有效抑制，其跨度范围为10.0-97.5和10.1-71.8 nM。有趣的是，芳基砜hydr 9在hCA I（SI：分别为39.4-250.3和26.0-149.9）和hCA II（SI：分别为19.6-57.1和13.0-34.2）上显示出对hCA IX和XII的最佳选择性。此外，根据US-NCI协议，评估了目标苯并呋喃对一组六十种癌细胞系的抗增殖活性。仅苯并呋喃5b和10b对某些癌细胞系具有选择性和中等的生长抑制活性。