Saeed Aamer, Imran Aqeel, Channar Pervaiz A, Shahid Mohammad, Mahmood Wajahat, Iqbal Jamshed
Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
Chem Biol Drug Des. 2015 Feb;85(2):225-30. doi: 10.1111/cbdd.12379. Epub 2014 Jul 10.
A small series of 2-(hetero(aryl)methylene) hydrazine-1-carbothioamides including two aryl derivatives was synthesized and tested for their inhibitory activity against urease. Compound (E)-2-(Furan-2-ylmethylene) hydrazine-1-carbothioamide (3f), having a furan ring, was the most potent inhibitor of urease with an IC50 value of 0.58 μM. Molecular modeling was carried out through docking the designed compounds into the urease binding site to predict whether these derivatives have analogous binding mode to the urease inhibitors. The study revealed that all of the tested compounds bind with both metal atoms at the active site of the enzyme. The aromatic ring of the compounds forms ionic interactions with the residues, Ala(440), Asp(494), Ala(636), and Met(637).
合成了一小系列包含两种芳基衍生物的2-（杂（芳基）亚甲基）肼-1-碳硫酰胺，并测试了它们对脲酶的抑制活性。具有呋喃环的化合物（E）-2-（呋喃-2-基亚甲基）肼-1-碳硫酰胺（3f）是脲酶最有效的抑制剂，IC50值为0.58μM。通过将设计的化合物对接至脲酶结合位点进行分子建模，以预测这些衍生物是否具有与脲酶抑制剂类似的结合模式。研究表明，所有测试化合物均与酶活性位点的两个金属原子结合。化合物的芳环与残基Ala（440）、Asp（494）、Ala（636）和Met（637）形成离子相互作用。
