Abstract
A novel ruthenium(III)–pyrimidine Schiff base was synthesized and characterized using different analytical and spectroscopic techniques. Molecular geometries of the ligand and ruthenium complex were investigated using the DFT-B3LYP level of theory. The quantum global reactivity descriptors were also calculated. Various biological and molecular docking studies of the complex are reported to explore its potential application as a therapeutic drug. Cytotoxicity of the complex was screened against cancer colorectal (HCT116), breast (MCF-7 and T47D), and hepatocellular (HepG2) cell lines as well as a human normal cell line (HSF). The complex effectively inhibited the tested cancer cells with variable degree with higher activity towards HepG2 (IC50 values were 29 μM for HepG2, 38.5 μM for T47D, 39.7 μM for HCT, and 46.7 μM for MCF-7 cells). The complex induced apoptosis and cell cycle arrest in the S phase of HepG2 cells. The complex significantly induced the expression of H2AX and caspase 3 and caspase 7 gene and the protein level of caspase 3, as well as inhibited VEGF-A and mTOR/AKT, SND1, and NF-kB gene expression. The molecular docking studies supported the increased total apoptosis of treated HepG2 cells due to strong interaction of the complex with DNA. Additionally, the possible binding interaction of the complex with caspase 3 could be responsible for the elevated activity of caspase 3–treated cells. The score values for the two receptors were −3.25 and −3.91 kcal/mol.
Subject
Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health
Cited by
11 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Structural investigations of new tridentate-phenylacetohydrazide Schiff base metal chelates: X-ray diffraction, Hirshfeld surface analyses, DFT, antibacterial and molecular docking studies;Journal of Molecular Structure;2024-03
2. In vivo anticancer study of sodium 2‐[(4‐oxidobenzylidene)amino]‐6H‐1,3,4‐thiadiazine‐5‐olate against Ehrlich ascites carcinoma via targeting PI3K/mTOR pathway;Chemical Biology & Drug Design;2024-01-23
3. New bivalent metal chelates based on an NO-donor Schiff base ligand: synthesis, structural characterization, DFT simulation, biological evaluation, and molecular docking analysis;Inorganic Chemistry Communications;2024-01
4. A novel ruthenium complex with 5-fluorouracil suppresses colorectal cancer stem cells by inhibiting Akt/mTOR signaling;Cell Death Discovery;2023-12-16
5. Anti-α-glucosidase, Anti-proliferative and Anti-enterovirus 71 Activity of Secondary Metabolites Identified from Grifola Frondosa;Plant Foods for Human Nutrition;2023-10-09