Islam Muhammad, Ullah Saeed, Khan Ajmal, Batool Zahra, Mali Suraj N, Gurav Shailesh S, Dahlous Kholood A, Mohammad Saikh, Hussain Javid, Al-Harrasi Ahmed, Shafiq Zahid
Department of Basic Sciences and Humanities (Chemistry), Muhammad Nawaz Sharif University of Engineering and Technology (MNSUET), 60000, Multan, Pakistan.
School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Tianjin, 300072, China.
Sci Rep. 2025 Jan 3;15(1):609. doi: 10.1038/s41598-024-83386-4.
Clinically significant problems such as kidney stones and stomach ulcers are linked to the activation of the urease enzyme. At low pH, this enzyme gives an ideal environment to Helicobacter pylori in the stomach which is the cause of gastric ulcers and peptic ulcers. In recent work, we have developed a library of 4-fluorocinnamaldehyde base thiosemicarbazones and assessed them for their potential against urease enzyme. The synthesized compounds displayed significant to moderate inhibition potential with IC values ranging from 2.7 ± 0.5 µM to 29.0 ± 0.5 µM. compound 3c displayed the highest inhibition potential followed by 3a and 3b. Two compounds of the series 3f and 3 g remained inactive against urease. The kinetic study of compound 3c exhibited a competitive type of inhibition with a K value of 3.26 ± 0.0048 µM. SAR analysis was also thoroughly done. Molecular docking was used to analyze the interaction pattern of each derivative, and the outcomes demonstrated that the compounds had excellent binding interactions with the active site.
临床上的重大问题，如肾结石和胃溃疡，都与脲酶的激活有关。在低pH值下，这种酶为胃中的幽门螺杆菌提供了理想的环境，而幽门螺杆菌是导致胃溃疡和消化性溃疡的原因。在最近的研究中，我们开发了一个4-氟肉桂醛基硫代半卡巴腙库，并评估了它们对脲酶的潜在作用。合成的化合物表现出显著到中等程度的抑制潜力，IC值范围为2.7±0.5 µM至29.0±0.5 µM。化合物3c表现出最高的抑制潜力，其次是3a和3b。该系列中的两种化合物3f和3g对脲酶仍然没有活性。化合物3c的动力学研究显示出竞争性抑制类型，K值为3.26±0.0048 µM。还对构效关系进行了深入分析。使用分子对接来分析每种衍生物的相互作用模式，结果表明这些化合物与活性位点具有良好的结合相互作用。
