Relationship Between Thermodynamic Parameters and Genotoxicity of Bioactive Phenolic Compounds

Background: The effects in health of food containing phenolic compounds require currently studies related to safety. It has been established that these compounds may exhibit dual activity (antioxidant/pro-oxidant effects). Aims: The current work is focused on an in silico study to determine the relationships between different thermodynamic parameters and genotoxicity (GT) of phenolic compounds, such as flavonoids, cinnamic acids and coumarins. Materials and Methods: It was modeled the influence of local and global parameters that characterize the structure (hydrophobic, steric, electronic, and logP properties) in the clastogenic capacity (chromosome aberration generated by DNA damage, due to its pro-oxidant activity). ChemDraw, MODESLAB and STATISTIC software were used. QSPR models were obtained using molecular descriptors based on the TOPSMODE approach. Results: Properties thatcan influence the genetic damage caused by the studied pro-oxidant compounds, expressed through different Multivariate Linear Regression (MLR) statistical models, were identified. It was shown that steric (Sterimol, L) and hydrophobic (π) properties presented greater influence than the electronic properties (Hammett constant, σ*). Conclusion: A decrease in the logP is associated with increased DNA damage by clastogenicity. From the local modulated properties it was shown that steric and hydrophobic properties influenced the activity.Hansch hydrophobicity constant was considered the one that most influenced the activity. The substituent that most affected the activity was the methoxy group. The results allow us to establish structure-toxicity relationships, important for design strategies to obtain nutraceuticals, functional food and novel drugs with the described phenolic compounds on their composition.

Author(s): Estela Guardado Yordi, Maria João Matos, Lourdes Santana, Eugenio Uriarte, Amaury Pérez Martínez and Enrique Molina Pérez

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