Seven furanochromene-quinoline derivatives containing a hydrazone linker were synthesized by condensing a furanochromene hydrazide with quinoline 2-, 3-, 4-, 5-, 6-, and 8-carbaldehydes, including 8-hydroxyquinoline-2-carbaldehye. Structure-activity correlations were investigated to determine the influence of the location of the hydrazone linker on the quinoline unit on SARS-CoV-2 M enzyme inhibition. The 3-, 5-, 6- and 8-substituted derivatives showed moderate inhibition of SARS-CoV-2 M with IC values ranging from 16 to 44 μM. Additionally, all of the derivatives showed strong interaction with the SARS-CoV-2 M substrate binding pocket, with docking energy scores ranging from -8.0 to -8.5 kcal/mol. These values are comparable to that of N3 peptide (-8.1 kcal/mol) and more favorable than GC-373 (-7.6 kcal/mol) and ML-188 (-7.5 kcal/mol), all of which are known SARS-CoV-2 M inhibitors. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) profiles indicate that the derivatives have good drug-likeness properties. Overall, this study highlights the potential of the furanochromene-quinoline hydrazone scaffold as a SARS-CoV-2 M inhibitor.

中文翻译：

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呋喃色烯-喹啉腙衍生物的合成、SARS-CoV-2主要蛋白酶抑制、分子对接和计算机ADME研究

通过呋喃苯并苯酰肼与喹啉2-、3-、4-、5-、6-和8-甲醛（包括8-羟基喹啉-2-甲醛）缩合合成了七种含有腙连接体的呋喃苯并喹啉衍生物。研究了结构-活性相关性，以确定喹啉单元上腙连接体的位置对 SARS-CoV-2 M 酶抑制的影响。 3、5、6 和 8 取代衍生物对 SARS-CoV-2 M 表现出中等抑制作用，IC 值范围为 16 至 44 μM。此外，所有衍生物均表现出与 SARS-CoV-2 M 底物结合袋的强烈相互作用，对接能量得分范围为 -8.0 至 -8.5 kcal/mol。这些值与 N3 肽（-8.1 kcal/mol）相当，并且比 GC-373（-7.6 kcal/mol）和 ML-188（-7.5 kcal/mol）更有利，所有这些都是已知的 SARS-CoV -2M抑制剂。此外，计算机吸收、分布、代谢和排泄 (ADME) 曲线表明该衍生物具有良好的药物样特性。总体而言，这项研究强调了呋喃苯并喹啉腙支架作为 SARS-CoV-2 M 抑制剂的潜力。