PDF(Pubmed)
Abstract：
A novel series of hydantoins incorporating phthalimides has been synthesised by condensation of activated phthalimides with 1-aminohydantoin and investigated for their inhibitory activity against a panel of human (h) carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms hCA I, hCA II, and hCA VII, secreted isoform hCA VI, and the transmembrane hCA IX, by a stopped-flow CO2 hydrase assay. Although all newly developed compounds were totally inactive on hCA I and mainly ineffective towards hCA II, they generally exhibited moderate repressing effects on hCA VI, VII, and IX with KIs values in the submicromolar to micromolar ranges. The salts 3a and 3b, followed by derivative 5, displayed the best inhibitory activity of all the evaluated compounds and their binding mode was proposed in silico. These compounds can also be considered interesting starting points for the development of novel pharmacophores for this class of enzyme inhibitors.
摘要：
通过将活化的苯二甲酰亚胺与1-氨基乙内酰脲缩合合成了一系列掺入苯二甲酰亚胺的乙内酰脲，并研究了其对一组人（h）碳酸酐酶的抑制活性（CA，EC4.2.1.1)：胞质同工型hCAI，HCAII,和HCAVII，分泌型hCAVI，和跨膜hCAIX，通过停流CO2水合酶测定。尽管所有新开发的化合物对hCAI完全无活性，对hCAII主要无效，它们通常对hCAVI表现出适度的抑制作用，VII,和IX的KIs值在亚微摩尔到微摩尔范围内。盐3a和3b，其次是衍生物5，显示出所有评估化合物的最佳抑制活性，并且在计算机上提出了它们的结合模式。这些化合物也可以被认为是开发此类酶抑制剂的新型药效团的有趣起点。
