Reaction Of Resveratrol With Hypohalous Acids And Binding Of Hydroxycinnamic Acids To Bovine Serum Albumin

Cancer chemopreventive activity of resveratrol, a phytoalexin found in a wide range of food products, was first described in 1997. Since then, it has attracted much attention as an excellent antioxidant and antitumor agent. It has been recognized that chronic inflammation correlates with increased risk of developing cancer. Resveratrol can not only suppress the cancer process directly but also prevent or delay the promotion and progression of many human cancers by inhibiting inflammation.Serum albumins are the most abundant proteins in human circulatory system. They possess varieties of physiological functions and play an important role in free ligands transport and storage. The studies of the interaction between drugs and serum albumins can provide useful information to interpret the structure and function of the protein. In addition, the studies can also reflect the metabolic process and the bioavailability of the drug.In Charpter 2, the reactions of resveratrol with hypohalous acids(the products of myeloperoxidase) at pH 7.4 were carried out and eight halogenated derivatives of resveratrol including seven novel compounds were obtained. Furthermore, the inhibitory effects of these compounds on red blood cell hemolysis as well as bacterial growth were assessed. It was found that all the compounds exhibited better anti-hemolytic activities than resveratrol. Toward Candida albicans,2-chloro- and 2-bromo-resveratrol were more active than fluconazole, which is a well-known antibacterial agent commonly used.In Chapter 3, we used NMR inversion recovery method in combination with NMR saturation transfer difference spectroscopy and fluorescence quenching spectra to investigate the interaction between six hydroxycinnamic acids(chlorogenic acid, caffeic acid, ferulic acid, sinapic acid, p-coumaric acid and m-coumaric acid) and bovine serum albumin. We found the experimental data of the two methods fit each other well, the binding ability between the six compounds and BSA followed the order:chlorogenic acid>caffeic acid>m-coumaric acid≥p-coumaric acid> ferulic acid>sinapic acid. In addition, from the STD data, it is proposed that the benzene ring and double bond moieties were in close contact with the BSA surface, whereas the carboxyl group was solvent-exposed and formed no direct contact with the protein. In Chapter 4, we also investigated the binding mode between two anthracyclines(adriamycin and epirubicin) andα1-acid glycoprotein by NMR inversion recovery method along with saturation transfer difference spectroscopy. We found the binding affinity for epirubicin-α1-acid glycoprotein system was higher than that of adriamycin-α1-acid glycoprotein system. Interestingly, the proton-5’ of neither adriamycin nor epirubicin had STD NMR effect, indicating that the bottom of the six-membered ring of the drug was in close proximity to the protein surface.