Department of Chemistry, School of Chemical and Life Sciences, New Delhi, India.
Neurofarba Department, Section of Pharmaceutical Chemistry, Università degli Studidi Firenze, Firenze, Italy.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2189126. doi: 10.1080/14756366.2023.2189126.
A series of 20 newly designed ()-1-(4-sulphamoylphenylethyl)-3-arylidene-5-aryl-1H-pyrrol-2(3H)-ones was synthesised and assessed as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors towards four human isoforms of pharmaceutical interest, that is, hCA I, II, IX and XII. The compounds displayed low to high nanomolar potency against all the isoforms. Introducing strong electron withdrawing groups at the position of the arylidene ring increased the binding affinity to the enzyme. All compounds showed acceptable pharmacokinetic range and physicochemical characteristics as determined by computational ADMET analysis. Density Functional Theory (DFT) calculations of were carried to gain understanding on the stability of the and isomers. The energy values clearly indicate the stability of isomer over isomer by -8.2 kJ mol. Our findings indicate that these molecules are useful as leads for discovering new CA inhibitors.
合成了一系列 20 种新设计的（）-1-（4-磺酰胺基苯乙基）-3-芳亚基-5-芳基-1H-吡咯-2(3H)-酮，并评估了它们对四种具有药物应用价值的人源碳酸酐酶（CA，EC 4.2.1.1）同工酶的抑制活性，即 hCA I、II、IX 和 XII。这些化合物对所有同工酶均表现出低至中等纳米摩尔的抑制活性。在芳亚甲基环的 位置引入强吸电子基团可以提高与酶的结合亲和力。所有化合物的药代动力学范围和物理化学特性均通过计算 ADMET 分析确定，可接受。通过密度泛函理论（DFT）计算对进行了计算，以了解 和 异构体的稳定性。能量值清楚地表明异构体比异构体更稳定，差值为-8.2 kJ/mol。我们的研究结果表明，这些分子可用作发现新型 CA 抑制剂的先导化合物。
