Aly Ashraf A, Abdallah Elham M, Ahmed Salwa A, Rabee Mai M, Abdelhafez El-Shimaa M N
Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt.
Medicinal Chemistry, Department, Faculty of Pharmacy, Minia University, El-Minia 61519 Egypt.
J Mol Struct. 2022 Oct 5;1265:133480. doi: 10.1016/j.molstruc.2022.133480. Epub 2022 Jun 9.
Substituted thiosemicarbazones derived by 2-quinolone were synthesized to investigate their complexation capability towards Cu(I), Cu(II) and Ni(II) salts. The structure of the complexes was established by ESI, IR and NMR spectra in addition to elemental analyses. Monodetate Cu(I) quinoloyl-substituted ligands were observed, whereas Ni(II) and Cu(II) formed bidentate-thiosemicarbazone derived by 2-quinolones. Subsequently, molecular docking was used to evaluate each analog's binding affinity as well as the inhibition constant (i) to RdRp complex of SARS-CoV-2. Docking results supported the ability of the tested complexes that potentially inhibit the RdRp of SARSCov-2 show binding energy higher than their corresponding ligands. Additionally, ADMET prediction revealed that some compounds stratify to Lipinski's rule, indicating a good oral absorption, high bioavailability good permeability, and transport biological membranes. Therefore, these metals-based complexes are suggested to be potentially good candidates as -covid agents.
合成了由2-喹诺酮衍生的取代硫代氨基脲，以研究它们对Cu(I)、Cu(II)和Ni(II)盐的络合能力。除了元素分析外，还通过电喷雾电离质谱（ESI）、红外光谱（IR）和核磁共振光谱（NMR）确定了配合物的结构。观察到单齿配位的Cu(I)喹诺酰取代配体，而Ni(II)和Cu(II)形成了由2-喹诺酮衍生的双齿硫代氨基脲。随后，使用分子对接来评估每个类似物对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的RNA依赖性RNA聚合酶（RdRp）复合物的结合亲和力以及抑制常数（i）。对接结果支持了测试的配合物具有潜在抑制SARS-CoV-2的RdRp的能力，其显示出的结合能高于相应的配体。此外，药物代谢及毒性预测（ADMET）显示一些化合物符合Lipinski规则，表明具有良好的口服吸收、高生物利用度、良好的渗透性以及跨生物膜转运能力。因此，这些金属基配合物被认为可能是作为抗新冠病毒药物的良好候选物。
