Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes

Hanan B Howsaui; Amal S Basaleh; Magda H Abdellattif; Walid M I Hassan; Mostafa A Hussien

doi:10.3390/biom11081138

Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes

Biomolecules. 2021 Aug 2;11(8):1138. doi: 10.3390/biom11081138.

Authors

Hanan B Howsaui¹, Amal S Basaleh¹, Magda H Abdellattif², Walid M I Hassan^{1

3}, Mostafa A Hussien^{1

4}

Affiliations

¹ Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
² Department of Chemistry, College of Sciences, Taif University, Al-Haweiah, P.O. Box 11099, Taif 21944, Saudi Arabia.
³ Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
⁴ Department of Chemistry, Faculty of Science, Port Said University, Port Said 42521, Egypt.

Abstract

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the K_b values ranged from 1 × 10⁶ to 3.33 × 10⁵ M^-1. The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).

Keywords: DFT; DNA binding; Schiff base; anticancer; molecular docking; uranyl complexes.

MeSH terms

Aldehydes / chemistry
Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology
Binding Sites
Cattle
Cell Line, Tumor
Coordination Complexes / chemical synthesis*
Coordination Complexes / metabolism
Coordination Complexes / pharmacology
DNA / chemistry
DNA / metabolism
Density Functional Theory
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Epithelial Cells / pathology
ErbB Receptors / chemistry
ErbB Receptors / metabolism
Humans
Inhibitory Concentration 50
Intercalating Agents / chemical synthesis*
Intercalating Agents / metabolism
Intercalating Agents / pharmacology
Kinetics
Molecular Docking Simulation
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Pyrazines / chemistry
Schiff Bases / chemical synthesis*
Schiff Bases / metabolism
Schiff Bases / pharmacology
Solubility
Uranium Compounds / chemistry
X-Linked Inhibitor of Apoptosis Protein / chemistry*
X-Linked Inhibitor of Apoptosis Protein / metabolism

Substances

Aldehydes
Antineoplastic Agents
Coordination Complexes
Intercalating Agents
Pyrazines
Schiff Bases
Uranium Compounds
X-Linked Inhibitor of Apoptosis Protein
XIAP protein, human
salicylaldehyde
DNA
calf thymus DNA
EGFR protein, human
ErbB Receptors