University of Alberta, Faculty of Pharmacy, Edmonton, Alberta, Canada T6G 2N8.
Bioorg Med Chem Lett. 2011 Oct 1;21(19):5892-6. doi: 10.1016/j.bmcl.2011.07.090. Epub 2011 Jul 30.
A series of compounds incorporating regioisomeric phenylethynylbenzenesulfonamide moieties has been investigated for the inhibition of four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. Inhibition between the low nanomolar to the milliomolar range has been observed against them, with several low nanomolar and tumor-CA selective inhibitors detected. The position of the sulfamoyl group with respect to the alkyne functionality, and the nature of the moieties substituting the second aromatic ring were the principal structural features influencing CA inhibition. The para-sulfamoyl-substituted derivatives were effective inhibitors of CA IX and XII, the meta-substituted regioisomers of CA I, IX and XII, whereas the ortho-substituted sulfonamides were weak inhibitors of CA I, II and IX, but inhibited significantly CA XII.
已经研究了一系列包含区域异构苯乙炔基苯磺酰胺部分的化合物，以抑制四种人碳酸酐酶（hCA，EC 4.2.1.1）同工酶，即 hCA I、II、IX 和 XII。对它们的抑制作用在纳摩尔到毫摩尔范围内，检测到了几种低纳摩尔和肿瘤-CA 选择性抑制剂。磺酰胺基相对于炔基官能团的位置以及取代第二个芳环的部分的性质是影响 CA 抑制的主要结构特征。对磺酰胺基取代的衍生物是 CA IX 和 XII 的有效抑制剂，间位取代的 CA I、IX 和 XII 的区域异构体，而对位取代的磺酰胺是 CA I、II 和 IX 的弱抑制剂，但显著抑制 CA XII。
