Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)–Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells

Amani F. H. Noureldeen (), Safa W. Aziz, Samia A. Shouman, Magdy M. Mohamed, Yasmin M. Attia, Ramadan M. Ramadan () and Mostafa M. Elhady
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Amani F. H. Noureldeen: Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Safa W. Aziz: Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Samia A. Shouman: Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 12613, Egypt
Magdy M. Mohamed: Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Yasmin M. Attia: Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 12613, Egypt
Ramadan M. Ramadan: Chemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Mostafa M. Elhady: Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt

IJERPH, 2022, vol. 19, issue 20, 1-21

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 (IC 50 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.

Keywords: ruthenium–Schiff base complex; DFT studies; antitumor activity; DNA damage; cell cycle arrest; apoptosis; molecular docking (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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