Natural Coumarins: QSTR Approaches Regarding Their Genotoxicity
Estela Guardado Yordi, Maria João Matos, Lourdes Santana, Eugenio Uriarte, Orlando Abreu and Enrique Molina Pérez
Abstract: 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 coumarins that come from several natural sources were studied. These coumarins belong to the chemical subclasses: simple coumarins, furocoumarins, dihydrofurocoumarins, pyranocoumarins, phenylcoumarins and biscoumarins. Thepre-selected database was formed taking into account topological-structural information, using molecular descriptors from the TOPSMODE approach. A virtual screening, that used a structure-clastogenic activity model and linear discriminant analysis (LDA) technique, was also performed. Several natural coumarins showed clastogenic activity in silico. For this family, the QSTR associated the probability of being active to the presence of hydroxy and methoxy groups in the molecules. It is of positive contribution of the fragment that forms the bay region of the pyranocoumarinic system. These in silico results may contribute to the safe design of new foods, nutraceuticals or drugs. It may also be important in the prevention of cancer, in which pathology these substances show pro-oxidant activity.
Keywords: Coumarins, clastogenic activity, pro-oxidant activity, TOPSMODE approach.
Pages: 241 – 257 | Full PDF Paper