新型偶氮咪唑衍生物对新冠病毒主要蛋白酶（M：6LU7）潜在抑制作用的合成、表征及计算研究

Synthesis, characterization and computational study on potential inhibitory action of novel azo imidazole derivatives against COVID-19 main protease (M: 6LU7).

作者信息

Chhetri Abhijit, Chettri Sailesh, Rai Pranesh, Mishra Dipu Kumar, Sinha Biswajit, Brahman Dhiraj

机构信息

Department of Microbiology, St. Joseph's College, Darjeeling-734104, India.

Department of Chemistry, St. Joseph's College, Darjeeling-734104, India.

出版信息

J Mol Struct. 2021 Feb 5;1225:129230. doi: 10.1016/j.molstruc.2020.129230. Epub 2020 Sep 18.

A series of six novel imidazole anchored azo-imidazole derivatives (L1-L6) have been prepared by the simple condensation reaction of azo-coupled ortho-vaniline precursor with amino functionalised imidazole derivative and the synthesized derivatives (L1-L6) have been characterized by different analytical and spectroscopic techniques. Molecular docking studies were carried out to ascertain the inhibitory action of studied ligands (L1-L6) against the Main Protease (6LU7) of novel coronavirus (COVID-19). The result of the docking of L1-L6 showed a significant inhibitory action against the Main protease (M) of SARS-CoV-2 and the binding energy (ΔG) values of the ligands (L1-L6) against the protein 6LU7 have found to be -7.7 Kcal/mole (L1), -7.4 Kcal/mole (L2), -6.7 Kcal/mole (L3), -7.9 Kcal/mole (L4), -8.1 Kcal/mole (L5) and -7.9 Kcal/mole (L6). Pharmacokinetic properties (ADME) of the ligands (L1-L6) have also been studied.

通过偶氮偶联的邻香草醛前体与氨基官能化咪唑衍生物的简单缩合反应，制备了一系列六种新型咪唑锚定偶氮咪唑衍生物（L1-L6），并通过不同的分析和光谱技术对合成的衍生物（L1-L6）进行了表征。进行了分子对接研究，以确定所研究的配体（L1-L6）对新型冠状病毒（COVID-19）的主要蛋白酶（6LU7）的抑制作用。L1-L6的对接结果显示对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的主要蛋白酶（M）具有显著的抑制作用，并且发现配体（L1-L6）与蛋白质6LU7的结合能（ΔG）值分别为-7.7千卡/摩尔（L1）、-7.4千卡/摩尔（L2）、-6.7千卡/摩尔（L3）、-7.9千卡/摩尔（L4）、-8.1千卡/摩尔（L5）和-7.9千卡/摩尔（L6）。还研究了配体（L1-L6）的药代动力学性质（ADME）。