British Biomedical Bulletin

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 prooxidant 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. Guardado Yordi et al ___________________________________________ ISSN-2347-5447 BBB[3][3][2015] 317-329 Introduction Phenolic compounds derived from the secondary metabolism of plants, and can be found in various alimentary sources. Among them, flavonoids and cinnamic acids are the most abundant in plant foods .Coumarin derivatives are describedas constituents of several classes of foods, such as cinnamon, ginger bread, green tea, chicory and fruits (bilberry and cloudberry).Some essential oils, as cassia leaf oil, cinnamon bark oil and lavender oil have high levels of them.. Therefore, flavonoids, in particular coumarins, and phenolic acids are of great interest due to their biological properties. Their physiological, bacteriostatic and anti-tumour activities make these families attractive for further backbone derivatization and screening as novel therapeutic agents . The coumarin derivatives have inhibitors as cellular proliferation potential in various carcinoma cell lines. Recently the presence of these compounds in diet is being widely studied because of their different benefits to human health, such as antioxidant activity. However, it has also been evidenced that many of these substances have pro-oxidant activity in various experimental systems, under certain conditions, such as high dosage or the presence of metal ions. Studies about this duality have been carried out. Such results lead to the necessity of continued studies to evaluate the phenolic compounds from the point of view of their possible "adverse effect" (according to the purpose of use), which is of particular attention during the design and development of new types of food (additives, functional foods andnutraceuticals), and even drugs. It is known that some of these phenolic substances can be genetically active, and therefore capable of interacting with DNA. These effects could be related to injuries that can take years to manifest. Also, there is a proved relationship between exposure to genotoxic substances (either occupational, accidental or due lifestyles) and increased risk of cancer. The potential exposure to genotoxic agents, both physical and chemical, can produce chromosomal aberrations, being these agents called clastogens . DNA damage is an indicator of exposure to these agents, and it is commonly measured by the breakage of single or double chains . It can be easily observed by structural changes in the metaphase of the cell cycle, which are caused by breakage (clastogenic processes) of unrepaired or poorly repaired DNA chains. This process is considered the endpoint of oxidative damage to DNA, in conjunction with mutations . The DNA damage, chromosome aberrations and disorder in metabolic functioning are important in the initiation of the carcinogenetic process, through generation of reactive oxygen species. There are reports of phenolic substances with clastogenicactivity. It has also been predicted by in silico studies that some substances reported to have pro-oxidant activity can be clastogenic . In order to predict the clastogenic activity of phenolic compounds with reported pro-oxidant activity, QSAR methods have been previously employed, and they have been interpreted, in structural terms, structure-activity relationships. This has allowed the identification of structural alerts associated with clastogenicity using the TOPSMODE approach. It has been reported the influence of different substituents on polyphenolic congeneric structures, in a topological substructural level. Research studies have allowed us to appreciate a Guardado Yordi et al ___________________________________________ ISSN-2347-5447 BBB[3][3][2015] 317-329                                                         6517 . 0 3 1123 . 0 5 0078 . 0 1 6689 . 1 2 0626 . 0 8 5 10 8263 . 3 5 5 10 8202 . 9 5 6 1