Correlations between molecular structure and biological activity in "logical series" of dietary chromone derivatives

Abstract

The research was conducted in the "logical series" of seven ligands: chromone, flavone, 3hydroxyflavone, 3,7-dihydroxyflavone, galangin, kaempferol and quercetin. Each subsequent ligand differs from the previous one, among others by an additional hydroxyl group. The studied chromone derivatives are plant secondary metabolites which play an important role in growth, reproduction, and resistance to pathogens. They are important food ingredients with valuable pro-health properties. The studies of the relationships between their molecular structure and biological activity facilitate searching for new chemical compounds with important biological properties not by trial and error, but concerning the impact of specific changes in their structure on the compound properties. Therefore several pectroscopic methods (FT-IR, FT-Raman, 1 H and 13 C NMR) were applied to study the molecular structure of the compounds in the series. Moreover the quantum-chemical calculations at B3LYP/6-311++G** were performed to obtained the theoretical NMR spectra, NBO atomic charge, global reactivity descriptors and thermodynamic parameters. The antioxidant activity of the compounds was tested in the DPPH and FRAP assays and the mechanism of antioxidant activity was discussed based on the results on theoretical calculations. The cytotoxicity of the ligands toward human epithelial colorectal adenocarcinoma Caco2 cells was estimated and correlated with the lipophilicity of the compounds. The principal component analyses (PCA) and hierarchical cluster analysis were used to study the dependency between the molecular structure of ligands and their biological activity. The experimental data were related to the theoretical ones. The found regular changes in physicochemical properties correlated well with the systematic changes in antioxidant and biological properties.

Caffeic Acid/Eu(III) Complexes: Solution Equilibrium Studies, Structure Characterization and Biological Activity

“…As part of a wider topic which aims to study the relationship between the molecular structure and the biological activity (microbial, cytostatic and antioxidant) of selected phenolic acids and their metal complexes [ 31 , 32 , 33 , 34 ], we present herein the study of the interaction of CFA towards Eu(III), and how the complexation influences the antimicrobial and the antioxidative properties of CFA. On a global perspective, we intend to contribute to a better understanding of how coordination with selected metals affects the molecular structure and distribution of the electronic charge of ligands, changing CFA biological activity, including their antioxidant properties.…”

Natural Cinnamic Acid Derivatives: A Comprehensive Study on Structural, Anti/Pro-Oxidant, and Environmental Impacts

“…Furthermore, there is much evidence that phenolics, in sufficiently high concentrations, may as well act as pro-oxidants, being able to start a pro-oxidant reaction through Fe(III)–Fe(II) reduction, resulting in the formation of hydroxyl radicals [ 12 , 13 ]. Current data confirm that even an insignificant change in the structure (number and substitution pattern of hydroxyl groups, charge distribution, or strength of the intramolecular hydrogen bonds) can rapidly affect the anti/pro-oxidant and cytotoxic effects of chemicals [ 1 , 14 , 15 ].…”

Drug Design Strategies for the Treatment of Viral Disease. Plant Phenolic Compounds and Their Derivatives

“…The antioxidant properties of phenolic compounds are determined, among others, by the position and number of hydroxyl groups in the aromatic ring, the degree of the electronic charge delocalization, the length of the conjugated double bond system, as well as the aromatic properties of the phenolic compounds, which are measured using the aromaticity indices and donor-acceptor properties described by the LUMO energy (Lowest Unoccupied Molecular Orbital) and HOMO energy (Highest Occupied Molecular Orbital) (Świderski et al, 2020). With increase of the HOMO orbital energy value, the better are electron donating activities (Lewandowski et al, 2020). The difference between the energy of HOMO-LUMO orbitals is known as the energy gap.…”

“…There is a dependency between IP and HOMO orbital energy-IP value decrease with the increase of HOMO orbital energy value, which facilitate the tendency to donate the electrons and leads to enhance the reactivity of compound (Kalinowska et al, 2020). On the other hand according to Lewandowski et al, very small values of ionization potential may contribute to alteration antioxidant properties into prooxidant (Lewandowski et al, 2020). Probably the type of metal cation influences the antioxidant properties of phenolic compounds.…”