Inhibitory action of newly synthesised 4-(2-(2-substituted-thio-4-oxoquinazolin-3(4H)-yl)ethyl)benzenesulfonamides compounds 2-13 against human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII, was evaluated. hCA I was efficiently inhibited by compounds 2-13 with inhibition constants (KIs) ranging from 57.8-740.2 nM. Compounds 2, 3, 4, and 12 showed inhibitory action against hCA II with KIs between 6.4 and 14.2 nM. CA IX exhibited significant sensitivity to inhibition by derivatives 2-13 with KI values ranging from 7.1 to 93.6 nM. Compounds 2, 3, 4, 8, 9, and 12 also exerted potent inhibitory action against hCA XII (KIs ranging from 3.1 to 20.2 nM). Molecular docking studies for the most potent compounds 2 and 3 were conducted to exhibit the binding mode towards hCA isoforms as a promising step for SAR analyses which showed similar interaction with co-crystallized ligands. As such, a subset of these mercaptoquinazolin-4(3H)-one compounds represented interesting leads for developing new efficient and selective carbonic anhydrase inhibitors (CAIs) for the management of a variety of diseases including glaucoma, epilepsy, arthritis and cancer.

中文翻译：

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探索包含4-乙基苯磺酰胺作为人类碳酸酐酶抑制剂的S-取代的2-巯基喹唑啉-4（3H）-的构效关系。

新合成的4-（2-（2-（2-取代-硫代-4-氧代喹唑啉-3（4H）-基）乙基））苯磺酰胺化合物2-13对人碳酸酐酶的抑制作用（CA，EC 4.2.1.1）（hCA）评估了同工型I，II，IX和XII。hCA I被化合物2-13有效抑制，抑制常数（KIs）为57.8-740.2 nM。化合物2、3、4和12对HICA II的抑制作用为KIs在6.4和14.2 nM之间。CA IX对衍生物2-13的抑制表现出显着的敏感性，KI值在7.1至93.6 nM之间。化合物2、3、4、8、9和12也对hCA XII发挥了有效的抑制作用（KIs范围为3.1至20.2 nM）。进行了最有效的化合物2和3的分子对接研究，以显示出与hCA亚型的结合模式，这是SAR分析的有前途的一步，显示出与共结晶的配体具有相似的相互作用。因此，这些巯基喹唑啉-4（3H）-one化合物的子集代表了开发新的高效选择性碳酸酐酶抑制剂（CAI）的有趣线索，这些抑制剂可用于治疗各种疾病，包括青光眼，癫痫，关节炎和癌症。