Novel chromone and xanthone derivatives: Synthesis and ROS/RNS scavenging activities

• A series of new chromone and xanthone derivatives were designed and synthesized.
• Most of the tested compounds displayed high in vitro ROS/RNS scavenging activity.
• A 7-hydroxychromone bearing a catechol moiety has emerged as the lead compound.

Chromones and xanthones are oxygen-containing heterocyclic compounds acknowledged by their antioxidant properties. In an effort to develop novel agents with improved activity, a series of compounds belonging to these chemical classes were prepared. Their syntheses involve the condensation of appropriate 2-methyl-4H-chromen-4-ones, obtained via Baker-Venkataraman rearrangement, with (E)-3-(3,4-dimethoxyphenyl)acrylaldehyde to provide the corresponding 2-[(1E,3E)-4-(3,4-dimethoxyphenyl)buta-1,3-dien-1-yl]-4H-chromen-4-ones. Subsequent electrocyclization and oxidation of these compounds led to the synthesis of 1-aryl-9H-xanthen-9-ones. After cleavage of the protecting groups, hydroxylated chromones and xanthones were assessed as scavenging agents against both reactive oxygen species (ROS) [superoxide radical (O2
• -), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen (1O2), and peroxyl radical (ROO
• )] and reactive nitrogen species (RNS) [nitric oxide (
• NO) and peroxynitrite anion (ONOO−)]. Generally, all the tested new hydroxylated chromones and xanthones exhibited scavenger effects dependent on the concentration, with IC50 values found in the micromolar range. Some of them were shown to have improved scavenging activity when compared with previously reported analogues, allowing the inference of preliminary conclusions on the structure–activity relationship.

Figure optionsDownload as PowerPoint slide