Bilal Hazrat, Ullah Saeed, Halim Sobia Ahsan, Khan Momin, Avula Satya Kumar, Alam Aftab, Zayed Eman Serry, El-Ghaiesh Sabah H, Ogaly Hanan A, Shah Zarbad, Khan Ajmal, Al-Harrasi Ahmed
Department of Chemistry, Bacha Khan University Charsadda Charsadda-24420 Khyber Pakhtunkhwa Pakistan
Department of Chemistry, Government Postgraduate College Dargai Malakand Pakistan.
RSC Adv. 2025 Mar 28;15(12):9510-9520. doi: 10.1039/d5ra00459d. eCollection 2025 Mar 21.
The overexpression of urease is the root cause of peptic ulcers and gastritis. Therefore, introducing new inhibitors against urease is a possible therapeutic approach to overcoming the pathogenesis; for instance, limiting the risk of development of urinary calculi. Moreover, glycation is the leading cause of several complications. Thus, in this study, we synthesized novel terephthalic dihydrazide analogues and evaluated their biological importance. These terephthalic dihydrazide analogues were characterized using advanced spectroscopic techniques, such as H NMR, C NMR, F NMR and HRMS (ESI), and FT-IR. Fortunately, 6 of the 11 synthesized compounds exhibited urease inhibitory capability, and 8 compounds exhibited anti-glycation capability. Compounds 13-14, 20 and 23 showed significant urease inhibition with IC values of 63.12 ± 0.28, 65.71 ± 0.40, 49.2 ± 0.49 and 51.45 ± 0.39 μM, respectively. Meanwhile, they exhibited potent anti-glycation activity with IC values of 67.53 ± 0.46, 68.06 ± 0.43, 48.32 ± 0.42 and 54.36 ± 0.40 μM, respectively. Molecular docking of active urease inhibitors showed their good binding at the entrance of the active site and good correlation with our results.
脲酶的过度表达是消化性溃疡和胃炎的根本原因。因此，引入新型脲酶抑制剂是克服发病机制的一种可能的治疗方法；例如，限制尿路结石形成的风险。此外，糖基化是多种并发症的主要原因。因此，在本研究中，我们合成了新型对苯二甲酰二肼类似物并评估了它们的生物学重要性。这些对苯二甲酰二肼类似物使用先进的光谱技术进行了表征，如氢核磁共振、碳核磁共振、氟核磁共振和高分辨质谱（电喷雾电离）以及傅里叶变换红外光谱。幸运的是，11种合成化合物中有6种表现出脲酶抑制能力，8种化合物表现出抗糖基化能力。化合物13 - 14、20和23显示出显著的脲酶抑制作用，其半数抑制浓度值分别为63.12 ± 0.28、65.71 ± 0.40、49.2 ± 0.49和51.45 ± 0.39 μM。同时，它们表现出强效的抗糖基化活性，其半数抑制浓度值分别为67.53 ± 0.46、68.06 ± 0.43、48.32 ± 0.42和54.36 ± 0.40 μM。活性脲酶抑制剂的分子对接显示它们在活性位点入口处具有良好的结合能力，并且与我们的结果具有良好的相关性。
