DNA/Protein Binding and Apoptotic-Induced Anticancer Property of a First Time Reported Quercetin–Iron(III) Complex Having a Secondary Anionic Residue: A Combined Experimental and Theoretical Approach

Abstract

A new quercetin-based iron(III) cationic complex [Fe(Qr)Cl(H2O)(MeO)] (complex 1) is created in the current study by condensation of quercetin with ferric chloride in the presence of Et3N. Comprehensive spectroscopic analysis and conductometric measurement are used to pinpoint complex 1. The generated complex’s +3-oxidation state has been verified by electron paramagnetic resonance (EPR) research. Density functional theory analysis was used to structurally optimize the structure of complex 1. Before biomedical use, a variety of biophysical studies are implemented to evaluate the binding capacity of complex 1 with DNA and human serum albumin (HSA) protein. The findings of the electronic titration between complex 1 and DNA, as well as the stunning fall in the fluorescence intensities of the HSA and EtBr-DNA/DAPI-DNA domain after complex 1 is gradually added, give us confidence that complex 1 has a strong affinity for both macromolecules. It is interesting to note that the displacement experiment confirms partial intercalation as well as the groove binding mechanism of the title complex with DNA. The time-dependent fluorescence analysis indicates that after interaction with complex 1, HSA will exhibit static quenching. The thermodynamic parameter values in the HSA–complex 1 interaction provide evidence for the hydrophobicity-induced pathway leading to spontaneous protein–complex 1 interaction. The two macromolecules’ configurations are verified to be preserved when they are associated with complex 1, and this is done via circular dichroism spectral titration. The molecular docking investigation, which is a theoretical experiment, provides complete support for the experimental findings. The potential of the investigated complex to be an anticancer drug has been examined by employing the MTT assay technique, which is carried out on HeLa cancer cell lines and HEK-293 normal cell lines. The MTT assay results validate the ability of complex 1 to display significant anticancer properties. Finally, by using the AO/PI staining approach, the apoptotic-induced cell-killing mechanism as well as the detection of cell morphological changes has been confirmed.

The Effect of Metal Ions (Fe, Co, Ni, and Cu) on the Molecular-Structural, Protein Binding, and Cytotoxic Properties of Metal Pyridoxal-Thiosemicarbazone Complexes

“…The discrepancy between these values and the experimental ∆G value is noticeable. The main reason is that BSA's crystallographic structure significantly differs from the one in the aqueous solution [46], as explained in the literature [50,51]. Furthermore, the complex structure of Fe-PLTSC included in the docking study contained chloride ions that are probably not bound to the central metal ion once dissolved.…”

Synthesis, Structural Characterization, Cytotoxicity, and Protein/DNA Binding Properties of Pyridoxylidene-Aminoguanidine-Metal (Fe, Co, Zn, Cu) Complexes

“…The differences between these values and the experimental ones are noticeable. One of the main reasons is the change in BSA structure when solvated by the water molecules and other ions of the phosphate buffer [50][51][52]. Moreover, complexes Cu-PLAG and Z-PLAG contain ligands loosely bound to the metal ion, and their exchange with the solvent molecules can be expected.…”

A multi-spectroscopic and molecular docking approach for DNA/protein binding study and cell viability assay of first-time reported pendent azide bearing Cu(II)-quercetin and dicyanamide bearing Zn(II)-quercetin complexes

“…It's interesting to note that it is a well-known anticancer agent and that its mechanism of cell death is also disclosed [ 24 , 25 ]. The use of cisplatin as an effective anticancer drug, inspires the scientific community to develop several metal-based compounds with effective biological applications [ [26] , [27] , [28] , [29] , [30] , [31] , [32] ]. At the same time, many quercetin-metal complexes are synthesized and inspected with respect to their DNA and HSA binding efficacy [ [33] , [34] , [35] , [36] ].…”