Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan.
Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
Bioorg Chem. 2014 Feb;52:1-7. doi: 10.1016/j.bioorg.2013.10.001. Epub 2013 Oct 30.
Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 μM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.
硫脲是合成各种杂环体系的非常通用的构建块，具有广泛的药理活性。取代苯甲酸被转化为相应的酰氯，然后将这些酰氯在丙酮中与硫氰酸钾反应，然后将反应混合物回流 1-2 小时，以良好的收率得到乙基 4-(3-苯甲酰硫脲基)苯甲酸硫脲。所有新合成的化合物都进行了脲酶抑制活性评估，发现它们是脲酶的有效抑制剂。化合物 1f 和 1g 被鉴定为最有效的脲酶抑制剂（IC50 分别为 0.21 和 0.13 μM），比标准抑制剂强 100 倍。进一步使用脲酶的晶体结构进行分子对接研究，以找出抑制剂与酶的结合模式。
