Búsqueda de nuevos compuestos bioactivos con esqueleto de naftoquinona

Resumen

Naphthoquinones are natural products that are widespread in nature and they generally contain hydroxyl and/or methyl groups as substituents. In addition to their properties as natural pigments, a broad range of biological activities have been described, including antifungal, phytotoxic, anti-inflammatory, antioxidant and anticancer properties. Among this family of compounds, there are three biologically active naphthoquinones that are the focus of the work described here: juglone (5-hydroxy-1,4-naphthoquinone), plumbagin (5-hydroxy-2-methyl-naphthoquinone) and lawsone (2-hydroxy-1,4-naphthoquinone). They are proposed as lead compounds for the design of more potent analogs and for structure-activity relationship (SAR) studies in the search for possible new natural herbicides. The physico-chemical properties were modified through the preparation of 74 derivatives in order to achieve this goal. They were evaluated in an initial general activity bioassay (etiolated wheat coleoptile bioassay) and compounds with the best activity profiles were selected and evaluated on STS (Standard Target Species) and weed bioassays to use these compounds as models in the development of natural herbicides. The effects produced were mostly stunting and necrosis caused by growth inhibition. Strong inhibitory effects were observed for compounds 4–6, 50–52, 74, 67 and 77. Furthermore, the evaluation of the cytotoxic activity of some derivatives was carried out to its possible application in the treatment of tumor processes. Finally, naphthoquinones (mainly shikonin derivatives) have been found in the root periderm extracts of several Boraginaceous plants. The biological activity and the abundance of these pigments in the roots extracts of E. plantagineum and E. gaditanum was performed obtaining differences depending on the location and date of collection. Acetylshikonin and dimethylacrylshikonin were present in the highest concentrations in extracts of both species and greatest overall activity was observed with E. gaditanum extracts. Strong correlations between time of collection, sampling location and bioactivity were identified. Furthermore, four main isohexenylnaphthazarins have been isolated and described for the first time in E. gaditanum root extracts.