This research is pursuing drug discovery efforts exploiting coumarins as core templates for novel antioxidants. Different novel coumarin derivatives with versatile substitution patterns were tested to define the molecular features required for a high antioxidant activity and hence lending some insight to the subsequent design and synthesis of more selective agents. Target compounds were evaluated for antioxidant activity using Bleomycin depended DNA damage method and the data obtained was represented by extent of DNA damage measured by increase in absorbance at 532 nm. Theoretical calculations of the HO. radical with the coumarin molecule were performed. Reaction pathways with C2, C3, C4 as the target carbon atoms and corresponding radical adducts were studied. Different activation energies of all adducts suggest that these reactions should occur differently and with rather high selectivity.