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

Manjushree Bera; Manik Das; Malay Dolai; Soumik Laha; Md Maidul Islam; Bidhan Chandra Samanta; Arindam Das; Indranil Choudhuri; Nandan Bhattacharyya; Tithi Maity

doi:10.1021/acsomega.2c05790

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

ACS Omega. 2022 Dec 20;8(1):636-647. doi: 10.1021/acsomega.2c05790. eCollection 2023 Jan 10.

Authors

Affiliations

¹ Department of Nutrition, Prabhat Kumar College, Contai, Purba Medinipur, Contai721404, India.
² Department of Chemistry, Prabhat Kumar College, Contai, Purba Medinipur, Contai721404, India.
³ IICB, Kolkata, Kolkata, 700032West Bengal, India.
⁴ Department of Chemistry, Aliah University, Kolkata700064, India.
⁵ Department of Chemistry, Mugberia Gangadhar Mahavidyalaya, Purba Medinipur, Contai721425, India.
⁶ Department of Chemistry, Jadavpur University, Kolkata700032, India.
⁷ Panskura Banamali College, Panskura, 721152West Bengal, India.

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.