Structure-radical scavenging activity relationship of alkannin/shikonin derivatives

Alkannins and shikonins (A/S) are naturally occurring isohexenylnaphthazarins (IHNs) of great interest in the field of life sciences due to their broad spectrum of biological properties and are used as food colourants in some countries. In the present study for the first time assessment of the radical scavenging activity of A/S and selected derivatives was carried out using the Crocin Bleaching Assay (CBA) and a modified DPPH assay. Exploration of structure-radical scavenging activity relationship (SAR) was approached with a wide range of A/S derivatives. To accomplish this task, a computational approach was also employed for the two enantiomers and other structurally related compounds. The findings indicated that the side chain –OH group at C-1′ has a positive effect to the radical scavenging properties of alkannin/shikonin by assisting hydrogen atom donation from this carbon atom. Thus, alkannin and shikonin were more potent than deoxyshikonin. Esterification of that hydroxyl group was critical for the activity of the respective compounds (acetyl-, isovaleryl- and β,β-dimethylacryl-shikonin). All of the examined IHN derivatives were found experimentally less potent scavengers than naphthazarin.