Coumarins are a group of phytochemicals with multiple applications in different fields, such as food and medicine. Many of their benefits are based on the different activities that they display, within which stand antioxidant properties. However, some conflicting evidences suggest the need to clarify or estimate the safety aspects and genotoxicity of this group of compounds. In this sense it has been shown in previous studies that some of them have presented pro-oxidant activity in vitro and clastogenic activity in silico. Therefore, in this paper chemical structures of natural coumarins that come from various natural sources were studied. This database became topological-structural information, using molecular descriptors from the TOPSMODE approach. A virtual screening was also held that used a model of structure-clastogenic activity relationship, and linear discriminant analysis (LDA) technique. The main results were interpreted in terms of safety.

The main etiological agents in dermatophytosis of human skin and nails are Trichophyton, in particular Trichophyton rubrum (T. rubrum) and Trichophyton mentagrophytes (T. mentagrophytes). A new series of twenty-three 3-and 4-arylcoumarins was synthesized and the antifungal activities against clinical isolates of T. rubrum and T. mentagrophytes were evaluated. Sixteen out of twenty-three molecules exhibited antifungal activity against one or both fungi strains. In some cases, the activity against T. rubrum has been comparable to fluconazole, one of the standards, being 8-methoxy-3-(4'-nitrophenyl) coumarin ( 16) the best compound within this series (minimum inhibitory concentration, MIC = 6.25 μg/mL). The preliminary structure-activity relationship study showed that the antifungal activity depends on the position and nature of the substitution patterns. The cytotoxicity of eleven compounds on D-384 (astrocytoma), A-549 (lung cancer) and RKO (colorectal cancer) cell lines was also performed. With the aim of deeply understand the potential of these molecules as hits to develop new drugs, the theoretical absorption, distribution, metabolism and excretion (ADME) properties of the active compounds were calculated.

Abstract. Drug discovery is a challenging task for researchers due to the complexity of biomolecules involved in pathologic processes. Design and development of efficient drugs is still urgent for several diseases.Cheminformatics tools are useful to better understand the interaction between new chemical entities and their targets. We studied a selected series of 3-arylcoumarins with antioxidant potential, and how their chemical features can contribute for the clastogenic activity. A virtual screening, based on the TOPSMODE approach, using a clastogenic model, was performed. The results suggest that the presence and position of hydroxyl groups in the scaffold is important for the activity. This communication is focused on cheminformatics, and its applications in drug effectiveness and safety.

The effects in health of food rich in phenols require currently studies related to safety. It has been shown that these compounds can present dual activity (antioxidant/pro-oxidant effects). In this sense, this work it is focused on an in silico study to determine the relationships of various thermodynamic parameters to genotoxicity (GT) of phenolic compounds: flavonoids, cinnamic acids and coumarins. The fundamental basis of the extra-thermodynamic methodology establishes that the structure of the bioactive molecule is a function of certain local and global properties. It was modeled the influence of local and global parameters that characterize the structure (hydrophobic, steric, electronic, and log P properties) relative to the clastogenic capacity (chromosome aberration generated by DNA damage due to its pro-oxidant activity). To achieve these objectives they were used ChemDraw, MODESLAB and STATISTIC software.They were identified properties influencing the genetic damage caused by the studied compounds with pro-oxidant activity, expressed through different Multivariate Linear Regression (MLR) statistical models. It was shown that steric (Sterimol, L) and hydrophobic (π) properties presented greater influence than the electronic properties (Hammett constant, σ*).Regarding the global property analysed, it was found that a decrease in the log P is associated with increased DNA damage by clastogenicity. The results allow us to produce an analysis of structure-toxicity relationship in designing strategies for nutraceuticals, functional foods and novel drug with such phenolic compounds on their structure.