Evaluation of the genotoxic, DNA-protective and antioxidant profile of synthetic alkyl gallates and gallotannins using in vitro assays.

New gallotanins, methyl 2,3,4,6-tetra-O-galloyl-α-D-glucoside (GGlc), methyl 2,3,4,6-tetra-O-galloyl-α-D-mannoside (GMan), and methyl 2,3,4-tri-O-galloyl-α-L-rhamnoside (GRham), have been synthesized in order to study the protective effects of synthetic polyphenols that are structurally related with natural compounds. Apart from spectral analysis, examination of antioxidant ability and protective efficiency showed the differences among newly prepared compounds and commercial antioxidants - gallic acid (GA), methyl gallate (MG), and octyl gallate (OG) applying radical scavenging 1,1-diphenyl-2-picryl-hydrazyl (DPPH), reducing power and iron-chelating assays. The genotoxicity and DNA-protective potential of tested compounds on human peripheral blood mononuclear cells (PBMCs) were evaluated using the single-cell gel electrophoresis (comet assay) and DNA-topology assay. Experimental data revealed that gallotannins GRham, GMan, and GGlc possess significant radical scavenging/antioxidant activities and manifest very low genotoxic effect on human PBMCs. Moreover, tested compounds considerably reduce the level of DNA damage induced by hydrogen peroxide or Fe-ions. The results imply that new synthetic gallotannins can be considered as nontoxic agents for subsequent design of new antioxidants with potential biomedical applications.