Green Chemistry Department, National Research Centre (NRC), P.O. Box 12622, DokkiCairo, Egypt.
Cellulose and Paper Department, National Research Centre, P.O. Box 12622, Giza, Egypt.
Sci Rep. 2023 Sep 4;13(1):14563. doi: 10.1038/s41598-023-41528-0.
In this study, the oxidation of microcrystalline cellulose using NaIO to yield the corresponding cellulose aldehyde utilized microwave irradiation as a green tool, the obtained cellulosic aldehyde was confirmed through spectral analysis and it has an active site to react with the synthesized uracil acetamide to afford the corresponding arylidene cellulosic MDAU(4), the latter compound which can easily due to presence of active CH=group behind a cyano group react with nitrogen nucleophile's and cyclized with hydrazine hydrate to give pyrazole cellulosic MDPA(5). The spectral analysis of the obtained cellulosic derivatives was confirmed with FT-IR, NMR, and SEM. Additionally, a neutral red uptake analysis has been used to investigate the cytotoxic activity of the cellulosic compounds MDAC(2), MDAU(4), and MDAP(5) against the cancer cells A549 and Caco2. After 48 h, Compound MDAU(4) had a stronger inhibitory effect on the growth of A549 and Caco2, compared to standard values. Then, using QRT-PCR, the appearance sites of the genes -Catenin, c-Myc, Cyclin D1, and MMP7 in A549 cells were examined. By reducing the expression levels of the Wnt signaling cascade genes -Catenin, c-Myc, Cyclin D1, and MMP7 when administered to A549 cells, compound MDAU(4) was shown in this investigation to be a viable candidate compared to lung cancer. Additionally, docking simulation was used to explore the uracil cellulosic heterocycles attached to different proteins, and computational investigations of these compounds looked at how well their physical characteristics matched the outcomes of their experiments.
在这项研究中,利用 NaIO 氧化微晶纤维素生成相应的纤维素醛,利用微波辐射作为绿色工具,通过光谱分析证实了所得到的纤维素醛,它具有与合成的尿嘧啶乙酰胺反应的活性位点,生成相应的芳基纤维素 MDAU(4),后者化合物由于氰基后面存在活性 CH=基团,容易与氮亲核试剂反应,并与水合肼环化,生成吡唑纤维素 MDPA(5)。所得到的纤维素衍生物的光谱分析通过 FT-IR、NMR 和 SEM 得到证实。此外,还使用中性红摄取分析来研究纤维素化合物 MDAC(2)、MDAU(4)和 MDAP(5)对 A549 和 Caco2 癌细胞的细胞毒性活性。48 小时后,与标准值相比,化合物 MDAU(4)对 A549 和 Caco2 的生长具有更强的抑制作用。然后,通过 QRT-PCR 检查 A549 细胞中基因 -Catenin、c-Myc、Cyclin D1 和 MMP7 的出现部位。通过降低 Wnt 信号级联基因 -Catenin、c-Myc、Cyclin D1 和 MMP7 在 A549 细胞中的表达水平,与肺癌相比,化合物 MDAU(4)在本研究中被证明是一种可行的候选药物。此外,还使用对接模拟来探索与不同蛋白质结合的尿嘧啶纤维素杂环,并对这些化合物进行计算研究,以查看它们的物理特性与实验结果的匹配程度。