Anti-inflammatory effects of flavonoids derivatives: Investigation of their structure activity relationship

Wood is a renewable source of natural molecules such as polyphenols that play an important role in biological processes. An analysis of byproducts from the pine forestry industry shows that flavonoids such as pinocembrin are widely found. Pinocembrin (5,7-dihydroxyflavanone) possesses a variety of biological properties such as anti-tumor, anti-oxidation and particularly anti-inflammatory activities. This flavanone represents an important class of natural products containing a 2-phenyl-benzopyran-4-one skeleton, which can be used as a starting material for the synthesis of bioactive molecules. In order to achieve rapid pharmacomodulations, flavanones can be obtained by a two-step synthesis route. The strategy used in this study starts with the synthesis of the intermediate chalcones by Claisen-Schmidt condensation, followed by an optimized cyclization to obtain the target flavanones. A series of flavanone derivatives was successfully synthesized with different functional groups on the two aromatic rings. Alternative access was considered for the cyclization of two derivatives by a photochemical route. All structures were established and confirmed by ¹H, ¹³C NMR and HRMS analyses. Anti-inflammatory activities of synthesized compounds were evaluated using an in vitro model of LPS-induced RAW264.7 macrophages and quantification of nitric oxide using the Griess assay. The screening results produced a structure-activity-relationship (SAR) that enabled identification of the structural requirements and essential functional groups for anti-inflammatory properties. This work confirmed flavanones as promising pharmacological candidates, which can be used as platform molecules for the future development of new pharmaceutical compounds.