Antioxidant Activities Of 2-phenylnaphthalenols, Hybrids With PMC And Methylated Resveratrol Derivatives

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), is a well-known natural antioxidant and cancer chemopreventive agent. Simplicity of the molecule in structure has resulted in extensive effort to find more active antioxidants and cancer chemoprevention agents by synthesizing its analogs. We synthesized and selected the compounds related to resveratrol including 2-phenylnaphthalenes, stilbene-chroman hybrids and methylated resveratrol derivatives, and studied their activity, structure-activity relationship and mechanism as antioxidants. The thesis includes the following details.(1) From the conjugation and rigidity point of view, we designed and synthesized a series of hydroxylated 2-phenylnaphthalenes. Their antioxidant acitivity and mechanism were characterized by ferric reducing antioxidant power (FRAP) assay, inhibition of oxidative damage of plasmid pBR322 DNA induced by AAPH, and DPPH radical-scavenging experiment. The main findings are as follows:(a) The compounds bearing ortho-dihydroxy groups possess significantly higher antioxidant activity than those without such groups including resveratrol; (b) Introduction of hydroxy groups on the naphthalene ring could efficiently improve antioxidant activity; (c) Their antioxidant mechanism depends on the used experimental systems. Specifically, FRAP assay corresponds to the electron-donating ability of the compounds, which proceed via electron transfer reaction. In ethyl acetate, their DPPH·-scavenging reaction occurs by direct hydrogen atom transfer, whereas in methanol that supports ionization, the reaction mechanism is primarily sequential proton loss electron transfer.(2) Hydroxylated stilbene-chroman hybrids and their parent molecules (resveratrol and PMC) displayed remarkable activity in the inhibition of the oxidative damage of bovine serum albumin and lysozyme induced by ONOO- and AAPH, respectively.(3) Methylated resveratrol derivatives were effective antioxidants in the AAPH-induced RBC hemolysis model, and were more active than resveratrol. Their anti-hemolysis activity could be due to demethylation by the demethylase from red blood cells, and electrophilic addition of lipid peroxy radicals to the double bond(s).