Anti-proliferative action, molecular investigation and computational studies of novel fused heterocyclic cellulosic compounds on human cancer cells

• Published in: International journal of biological macromolecules Vol. 222; pp. 3077 - 3099
• Main Authors: Elsayed, Ghada H., Dacrory, Sawsan, Fahim, Asmaa M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2022
• Subjects: Anti-proliferative activity; Computational studies; Heterocycle's cellulose; Molecular investigation; Molecular modeling docking; Heterocycle's cellulose; Computational studies; Molecular investigation; Anti-proliferative activity; Molecular modeling docking
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.10.083

Reactivity of MCEC (3) with diazonium chloride, DMF-DMA and NH2NH2 to afford fused heterocyclic cellulosic derivative which confirmed through spectral analysis. Also, the cellulosic compounds were evaluated their growth inhibitory activity contra cancer cells A549 and Caco2 using neutral red uptake assay. Compounds, MCEN(6), MCPT(5a), MCPT(5b) showed better growth inhibitory activity on A549 and Caco2 growth compared to control values. While compound MCPY(7) exerted the best cytotoxic activity against A549 cells after 48 h. The expression levels of HIF-1α, β-Catenin, MYC, Cyclin D1 and MMP7 genes in A549 cells were examined using QRT-PCR. The compounds MCEN(6) and MCPY(7) down regulated levels of β-Catenin, MYC, Cyclin D1 and MMP7 genes and up-regulated levels of HIF-1α when treated with A549 cells compared to control values. Also, these biological studies confirmed through docking stimulation with different proteins and showed least binding energy with amino acids and attached with NH2 and OH of cellulose with hydrogen bond interaction. Moreover, optimization of compounds using DFT/6-311(G) showed the stability of them and identifies their physical descriptors which showed excellent correlation with experimental results. Noteworthy, compounds, MCEN(6) and MCPY(7) were most promising anticancer agents against lung cancer through the regulation of apoptosis, cell cycle, proliferation, progression, chemo-resistance, and angiogenesis. [Display omitted]