This work describes the synthesis of eight different 6-nitro-1,4-disubstituted-quinoxaline-2,3‑dione derivatives (4a-h). The starting material, 6-nitroquinoxaline-2,3‑dione 3 was prepared by reacting 4-nitro-o-phenylenediamine 1 with oxalic acid 2 at reflux in hydrochloric acid. Compound 3 was alkylated with various alkyl halides under solid-liquid phase transfer catalysis (PTC) to give the dialkyl quinoxalines (4a-h). The structures of all compounds obtained were elucidated based on spectroscopic measurements: 1H, 13C NMR, MS and UV spectroscopy and confirmed by single-crystal X-ray diffraction studies in the case of 4a, 4b, 4f, and 4h. The geometrical parameters and spectral data were also compared with those of a DFT geometry optimization and molecular orbital calculation at the B3LYP/6–311++G (d, p) level of theory. The closest contacts between the molecules of the four structures were investigated by analyzing their Hirshfeld surfaces and docking investigations in the protein EGFR (pdbid: 4HJO). Moreover, the experimental results are correlated to the calculated ones and showed great compatibility. Cell proliferation was used to measure the immunomodulatory activity of 4a-h compared to a control consisting only of normal cells cultured alone to determine their antiproliferative screening which concluded that the quinoxaline derivatives 4c, 4d, 4f and 4g showed immunomodulatory potential.

中文翻译：

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新型 6-硝基喹喔-2,3-二酮衍生物的实验和理论研究：合成、表征、DFT 计算、ADME 分析、Hirshfeld 表面计算、分子对接研究和抗增殖评价


这项工作描述了八种不同的 6-硝基-1,4-二取代-喹喔啉-2,3-二酮衍生物 （4a-h） 的合成。起始材料 6-硝基喹啉-2,3-二酮 3 是通过 4-硝基-邻苯二胺 1 与草酸 2 在盐酸中回流反应制备的。化合物 3 在固液相转移催化 （PTC） 下与各种烷基卤化物烷基化，得到二烷基喹啉 （4a-h）。获得的所有化合物的结构均根据光谱测量进行阐明：1H、13C NMR、MS 和 UV 光谱，并在 4a、4b、4f 和 4h 的情况下通过单晶 X 射线衍射研究证实。还将几何参数和光谱数据与 B3LYP/6–311++G （d， p） 理论水平的 DFT 几何优化和分子轨道计算的数据进行了比较。通过分析它们的 Hirshfeld 表面和蛋白质 EGFR （pdbid： 4HJO） 的对接研究，研究了四种结构的分子之间的最紧密接触。此外，实验结果与计算结果相关联，并显示出很好的兼容性。与仅由单独培养的正常细胞组成的对照相比，细胞增殖用于测量 4a-h 的免疫调节活性，以确定其抗增殖筛选，得出结论喹喔啉衍生物 4c、4d、4f 和 4g 显示出免疫调节潜力。