Akash Muhammad, Rana Nehal, Aslam Sana, Ahmad Matloob, Saif Muhammad Jawwad, Asghar Aneeza, Sultan Sadia, Al-Hussain Sami A, Liaqat Afifa, Zaib Sumera, Zaki Magdi E A
Department of Chemistry, Government College University Faisalabad, Faisalabad, Pakistan.
Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, Pakistan.
Front Chem. 2024 Aug 6;12:1423385. doi: 10.3389/fchem.2024.1423385. eCollection 2024.
The urease enzyme is recognized as a valuable therapeutic agent for treating the virulent bacterium because of its pivotal role in aiding the colonization and growth of the bacterium within the gastric mucosa. In order to control the harmful consequences of bacterial infections, urease inhibition presents itself as a promising and effective approach. The current research aimed to synthesize pyridylpiperazine-based carbodithioate derivatives and that could serve as potential drug candidates for preventing bacterial infections through urease inhibition. The synthesized carbodithioate derivatives and were explored to assess their ability to inhibit the urease enzyme after their structural explication by gas chromatography-mass spectrometry (GC-MS). In the evaluation with thiourea as a standard drug, it was observed that all the synthesized compounds exhibited significant inhibitory activity compared to the reference drug. Among the compounds tested, (bearing an o-tolyl moiety) emerged as the most effective inhibitor, displaying strong urease inhibition with an IC value of 5.16 ± 2.68 μM. This IC value is notably lower than that of thiourea (23 ± 0.03 μM), indicating the significantly most potent potential of inhibition. In molecular docking of within the active site of urease, numerous noteworthy interactions were identified.
脲酶被认为是治疗这种致病菌的一种有价值的治疗剂，因为它在帮助细菌在胃黏膜内定植和生长方面起着关键作用。为了控制细菌感染的有害后果，脲酶抑制是一种有前景且有效的方法。当前的研究旨在合成基于吡啶基哌嗪的二硫代碳酸酯衍生物，这些衍生物可作为通过抑制脲酶来预防细菌感染的潜在候选药物。在通过气相色谱 - 质谱联用（GC - MS）对合成的二硫代碳酸酯衍生物进行结构解析后，对其抑制脲酶的能力进行了探索评估。在用硫脲作为标准药物进行的评估中，观察到与参比药物相比，所有合成化合物均表现出显著的抑制活性。在所测试的化合物中，（带有邻甲苯基部分）成为最有效的抑制剂，其对脲酶的抑制作用很强，IC值为5.16±2.68μM。该IC值明显低于硫脲的IC值（23±0.03μM），表明其具有显著更强的抑制潜力。在脲酶活性位点内进行分子对接时，发现了许多值得注意的相互作用。
