Three dihydroxy-4-methylcoumarin (DHMC) derivatives, namely 7,8-DHMC, 6,7-DHMC and 5,7-DHMC alone and complexed with Fe(III) and ADP have been tested for their antioxidative potential. Chemical speciation studies and formation constants reveal the formation of strong DHMC-Fe-ADP (1:1:1) ternary complex. In vitro studies were done for their antioxidative property by scavenging the superoxide radicals (O2*-) generated by xanthine + xanthine oxidase (XO) reaction. The IC50 values for 7,8-DHMC, 6,7-DHMC and 5,7-DHMC and their ternary complexes with Fe(III)-ADP worked out to be 34.0 microM, 62.0 microM, 8.80 mM and 10.5, 11.5 and 148.5 microM, respectively. The results indicate that O2*- scavenging potential of all the three DHMCs increased significantly after forming the ternary complex with Fe(III) and ADP. The structure activity relationship studies suggest that the introduction of hydroxyl group at 7th and 8th positions in the coumarins, irrespective of Fe(III)-ADP complexation, increases the antioxidative efficacy. No change in uric acid production in the reactions done for all studies further reveals that the coumarin derivatives and their complexes were the only causative factors for O2*- scavenging and not the suppression of the enzyme, xanthine oxidase.
Previously, we have reported that aurintricarboxylic acid (ATA) is one of the most potent inhibitors of the DNA binding of transcription factor NF-kappaB. We now report the NF-kappaB-DNA binding inhibitory activity of ATA analogues. An electrophoretic mobility shift assay has shown that bromopyrogallol red (BPR) is the most effective inhibitor of NF-kappaB-DNA binding among the studied analogues. The molecular modeling studies showed that BPR makes a strong network of hydrogen bonds with the DNA-binding region of the p50 subunit of NF-kappaB and has electronegative potential on its peripheral surface. Because zinc has been reported to influence the DNA binding of NF-kappaB, the interaction of these analogues with zinc was studied. Chemical speciation and formation-constant studies showed that BPR forms the most stable 1:1 complex with zinc. BPR has also been found to be the most potent antioxidant among the studied analogues.
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