In the current work, we adopted the tail/dual tail approaches to design and synthesize the benzenesulfonamide derivatives 6a-b, 8, 10a-b, 12a-b, 14, and 16 as new SLC-0111 analogs endowed with carbonic anhydrase (CA) inhibitory activity. All the prepared benzenesulfonamide derivatives were tested for their inhibitory action towards hCA isoforms; hCA I, II, IX, and XII. The results revealed their ability to affect the examined isoforms in variable degrees with K_I ranges: 49.3–6459 nM for CA I, 5.1–4171 nM for CA II, 9.4–945.1 nM for CA IX, and 5.2–1159 nM for CA XII. As expected, appending a second hydrophilic tail (ethanolamine) in compound 16 significantly enhanced the inhibitory activities towards hCA IX and hCA XII isoforms by about 5-fold in comparison to its single tail analogue 6c (K_I = 51.5 and 28.2 nM for 6c vs. 10.2 and 5.2 nM for 16, respectively). Moreover, SAR analysis pointed out the significance of grafting the sulfamoyl functionality at para-position, as well as the incorporation of a bulky hydrophobic tail for CA inhibitory activity. The most potent hCA IX inhibitors (6f and 16) displayed efficient cell growth inhibitory activity against breast cancer cell lines; T-47D (IC₅₀ = 19 and 10.9 μM, respectively) and MCF-7 (IC₅₀ = 7.5 and 5.7 μM, respectively).

在目前的工作中，我们采用尾/双尾方法设计并合成了苯磺酰胺衍生物6a-b 、 8、10a -b 、 12a-b 、 14和16 ，作为赋予碳酸酐酶（CA）的新SLC-0111类似物。 ）抑制活性。测试了所有制备的苯磺酰胺衍生物对hCA亚型的抑制作用； hCA I、II、IX 和 XII。结果显示它们能够以不同程度影响受检同种型， K _I范围为：CA I 49.3–6459 nM，CA II 5.1–4171 nM，CA IX 9.4–945.1 nM，CA XII 5.2–1159 nM 。正如预期的那样，与单尾类似物6c相比，在化合物16中附加第二个亲水尾（乙醇胺）显着增强了对 hCA IX 和 hCA XII 亚型的抑制活性约 5 倍（ 6c的K _I = 51.5 和 28.2 nM） 16分别为 10.2 和 5.2 nM）。此外，SAR分析指出了在对位接枝氨磺酰基官能团以及并入大的疏水尾部对于CA抑制活性的重要性。最有效的 hCA IX 抑制剂（ 6f和16 ）对乳腺癌细胞系表现出有效的细胞生长抑制活性； T-47D（IC ₅₀分别为 19 和 10.9 μM）和 MCF-7（IC ₅₀分别为 7.5 和 5.7 μM）。