Scavenging Activity of C4-Hydroxyphenyl- and Polyhydroxyphenyl-1,4- Dihydropyridines Toward Free Radicals

The radical-scavenging ability of synthesized C4-phenolic-substituted 1,4-dihydropyridines (1,4-DHPs) toward 2,2-diphenyl-1-picrylhydrazyl (DPPH •) and alkyl/alkylperoxyl ABAP-derived radicals at pH 7.4 was assessed by UV-visible spectroscopy. Reactivity of 1,4-DHPs toward DPPH • was measured by following the decay of the absorption corresponding to the radical ® max at 525 nm, permitting the calculation of EC 50, t EC50, and antiradical efficiency values. Pseudo-first-order kinetic rate constants for the reactivity between the C4-phenolic-substituted 1,4-DHP compounds and alkyl/alkylperoxyl ABAP-derived radicals were followed by the decrease in ® max at 356 nm corresponding to 1,4-DHP moiety. C4-phenolic-substituted 1,4-DHPs were more reactive toward alkyl free radicals than the other tested radicals. The 3,4,5-trihydroxyphenyl-1,4-DHP was the most reactive derivative toward this radical with a kinetic rate constant value of 513.2 s -1. Also, this derivative was the most effective toward the DPPH • radical with the lowest EC 50 value (5.08 ?M). Comparative studies revealed that synthesized 1,4-DHPs were more reactive than commercial 1,4-DHPs. The scavenging mechanism involves the contribution of both pharmacophores, that is, hydroxyphenyl and 1,4-DHP rings, which was supported by the identification of the reaction products. Copyright © 2012 Wiley Periodicals, Inc.