Ahmad Sajjad, Khan Momin, Alam Aftab, Ajmal Amar, Wadood Abdul, Khan Azim, AlAsmari Abdullah F, Alharbi Metab, Alshammari Abdulrahman, Shakoor Abdul
Department of Chemistry, Abdul Wali Khan University Mardan-23200 Pakistan
Department of Chemistry, University of Malakand Chakdara Lower Dir 18800 Pakistan.
RSC Adv. 2023 Aug 29;13(37):25717-25728. doi: 10.1039/d3ra03841f.
In this study, twenty eight novel oxadiazole derivatives (5-32) of the marketed available non-steroidal anti-inflammatory drug (NSAID), ()-flurbiprofen (1), were synthesized I mediated cyclo-addition reaction in better yields. The synthesized hydrazone-Schiff bases were cyclized with iodine by using potassium hydroxide as a base in DMSO solvent to obtain oxadiazole derivatives (5-32). Structures of the synthesized products were confirmed with HR-ESI-MS, H-NMR spectroscopy and CHN analysis. After structure confirmations all analogs were evaluated for urease () inhibitory activity. Amongst the series, fourteen compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 were found to be excellent inhibitors of urease enzyme, having IC values of 12 ± 0.9 to 20 ± 0.5 μM, better than the standard thiourea (IC = 22 ± 2.2 μM), whereas the remaining fourteen derivatives displayed good to moderate activity. The study was executed to analyse the interaction between the active site of the enzyme (urease) and the produced compounds. The docking study revealed that compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 had lower docking scores than the standard compound thiourea and revealed better interactions with the urease enzyme.
在本研究中，以市售的非甾体抗炎药（NSAID）（）-氟比洛芬（1）为原料，通过环加成反应以较高产率合成了28种新型恶二唑衍生物（5 - 32）。合成的腙 - 席夫碱在二甲基亚砜（DMSO）溶剂中以氢氧化钾为碱与碘环化，得到恶二唑衍生物（5 - 32）。通过高分辨电喷雾电离质谱（HR - ESI - MS）、氢核磁共振光谱（H - NMR）和元素分析（CHN）对合成产物的结构进行了确证。结构确证后，对所有类似物进行了脲酶（）抑制活性评估。在该系列化合物中，发现14种化合物20、26、30、24、21、16、28、31、32、7、19、13、10和6是脲酶的优良抑制剂，其半数抑制浓度（IC）值为12±0.9至20±0.5μM，优于标准品硫脲（IC = 22±2.2μM），而其余14种衍生物表现出良好至中等活性。开展该研究以分析酶（脲酶）活性位点与所生成化合物之间的相互作用。对接研究表明，化合物20、26、30、24、21、16、28、31、32、7、19、13、10和6的对接分数低于标准化合物硫脲，并且与脲酶显示出更好的相互作用。
