Anti-proliferative activity, molecular genetics, docking analysis, and computational calculations of uracil cellulosic aldehyde derivatives

Abstract

In this study, the oxidation of microcrystalline cellulose using NaIO4 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 control cells. Then, using QRT-PCR, the expression levels of the genes β-Catenin, c-Myc, Cyclin D1, and MMP7 in A549 cells were examined. By reducing the expression levels of the Wnt signaling cascade genes (β-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.