Atasever Arslan Belkis, Kaya Büşra, Şahin Onur, Baday Sefer, Saylan Cemil Can, Ülküseven Bahri
Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Üsküdar University, Istanbul, Turkey.
Department of Chemistry, Engineering Faculty, Istanbul University-Cerrahpasa, 34320 Avcilar, Istanbul, Turkey.
J Mol Struct. 2021 Dec 15;1246:131166. doi: 10.1016/j.molstruc.2021.131166. Epub 2021 Jul 22.
The discovery of new inhibitors that can be used in the treatment of viral diseases, including Covid-19, is an area open to research, and there is a need for innovative compounds with increased efficiency that provide inhibition by suppressing enzyme, and receptor mechanisms. The iron(III) and nickel(II) complexes were synthesized by template condensation of 4-methoxy-salicylaldehyde with S-methylthiosemicarbazone derivatives of 1,1,1-trifluoroacetylacetone (for ) and methylacetoacetate (for ). The complex structures having NO-chelating thiosemicarbazidato ligand were identified by analytical, spectroscopic, and X-ray crystallography results. Coordination environment of iron(III) center in complex has a distorted square pyramidal geometry consisting of the NO donor set and a chlorine atom, while that of is square plane with the set. Inhibitory effect of compound against SARS-CoV-2 virus specific 3C-like protease enzyme was investigated experimentally. It was determined that the highest inhibition concentration of was 100 μM. Percent inhibition activity at this concentration was on average 30.62 ± 3.809%. Binding of both compounds to the 3C-like protease enzyme specific to the SARS-CoV-2 virus was analyzed using docking calculations. As a result of the docking calculation of , it has been observed that the compound has a binding energy of -7.4 kcal / mol to 3CL-like protease. It has been observed that the protein amino acids GLY143, THR26, and ASN142 contribute to the high binding affinity of the . The experimental and theoretical results obtained for the two complexes support each other.
发现可用于治疗包括新冠病毒病（Covid - 19）在内的病毒性疾病的新型抑制剂，是一个有待研究的领域，需要具有更高效率的创新化合物，通过抑制酶和受体机制来发挥抑制作用。通过4 - 甲氧基水杨醛与1,1,1 - 三氟乙酰丙酮的S - 甲基硫代氨基脲衍生物（用于 ）和乙酰乙酸甲酯（用于 ）的模板缩合反应合成了铁（III）和镍（II）配合物。通过分析、光谱和X射线晶体学结果确定了具有NO - 螯合硫代氨基脲配体的配合物结构。配合物 中铁（III）中心的配位环境具有由NO供体组和一个氯原子组成的扭曲四方锥几何构型，而 的配位环境是具有该组的平面正方形。实验研究了 化合物对SARS-CoV-2病毒特异性3C样蛋白酶的抑制作用。确定 的最高抑制浓度为100 μM。该浓度下的抑制活性百分比平均为30.62±3.809%。使用对接计算分析了这两种化合物与SARS-CoV-2病毒特异性3C样蛋白酶的结合情况。通过对 的对接计算结果，观察到该化合物与3CL样蛋白酶的结合能为 - 7.4 kcal / mol。观察到蛋白质氨基酸GLY143、THR26和ASN142有助于 的高结合亲和力。两种配合物获得的实验和理论结果相互支持。
