Synthesis And Antioxidant Properties Of α-pyridoin And Its Derivatives

A large body of clinical and experimental evidence shows that reactive oxygen species (ROS) and free radicals are involved in many pathological conditions such as cancer, aging and atherosclerosis, and that antioxidants may have beneficial effects in protecting against these diseases. Thus, the role of antioxidants has attracted much attention. In order to find more active antixidants we synthesized:a-pyridoin (1) and its 5,5'-or 6,6'-bis-substituted derivatives (2-7) and hydroxyl-substituted Schiff bases (1-8), and compared their capacity to scavenge galvinoxyl radical (GO'), protect human red blood cells (RBCs) from oxidative haemolysis and their antiproliferative effects on human hepatoma HepG2 cells. In addition, we also studied the interaction mechanism and the structure-activity relationship between bovine serum albumin (BSA) and phenolic acids or hydroxyl-substituted Schiff bases.1) We synthesized a-pyridoin (1) and its 5,5'-or 6,6'-bis-substituted derivatives (2-7) using the benzoin condensation and compared their capacity to scavenge GO'and protect human RBCs from oxidative haemolysis. It was found that compounds with methyl or methoxy group in the 5-position exhibit significantly higher GO'-scavenging and anti-haemolysis activities than other derivatives and vitamin C. Kinetic analysis of GO'-scavenging reaction and the effect of added base on the reaction rate revealed that in ethyl acetate, the reaction occurs primarily by the direct hydrogen atom transfer (HAT mechanism). However, in ethanol that supports ionization, the kinetics of the process is mostly governed by sequential proton loss electron transfer (SPLET mechanism).2) Eight hydroxyl-substituted Schiff bases with the different number and position of hydroxyl group on the two asymmetric aromatic rings (A and B rings) were prepared by the reaction between the corresponding aromatic aldehyde and aniline. Their antioxidant effects against GO in ethyl acetate and methanol, and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced DNA strand breakage, and their antiproliferative effects on human hepatoma HepG2 cells, were investigated. Structure-activity relationship analysis demonstrates that o-dihydroxyl groups on the aromatic A ring and 4-hydroxyl group attached to the aromatic B ring contribute critically to the antioxidant and antiproliferative activities.3) The Interaction of phenolic acids and BSA was studied by fluorescence quenching spectra and NMR methodology. The binding constants KA and the number of binding sites n between phenolic acids and BSA were calculated by Stern-Volmer equation and their thermodynamic parameters were also calculated according to Vant's Hoff equation. The fluorescence quenching mechanism and binding capacity model were explained by the thermodynamic analyses. Chlorogenic acid had greater affinity for BSA than other derivatives with the binding constant and the number of binding sites being 81.9×104 L·mol-1 and 1.2, respectively, This is consistent with the result by NMR methodology. The normalized affinity index for chlorogenic acid-BSA systems, [AN]TL is 1.15×105 L·mol-1·s-1, indicates that chlorogenic acid exhibits the strongest BSA-binding activity among the phenolic acids examined.