Synthesis And Antioxidant Activities Of The Schiffbase Derivatives Containing Phenol Or Coumarin

Antioxidants have been widely concerned because of their important physiologic function in living organisms'anti-aging, disease prevention and immune regulation. The design and development of antioxidants having important, functional biological activity is one of the current focuses in biochemical and medicinal chemistry research fields. Based on the research background, this paper is divided in four parts: Synthesis and scavenging activities of the schiffbase derivatives containing phenol; Study on chelation abilities with Cu2+,Fe2+,Fe3+ and DNA of the schiffbase derivatives containing phenol; Synthesis and scavenging activities against DPPH-, ABTS+·,·OH and O2-·free radical of the coumarins derivatives; Study on chelation abilities with Cu2+,Fe2+,Fe3+,DNA and BSA of the coumarins derivatives.(Ⅰ) According to the principle of bioisosterism and the structure analysis of resveratrol which has excellent antioxidant activity, ten Schiff bases derivatives 1-5 containing phenol were synthesized and their free radical scavenging activities against DPPH·and ABTS+-free radical were evaluated. The result shows that the compounds exhibites good scavenging activities on DPPH·and ABTS+-free radical. The IC50 of compound 3a is 10.83μM, and thus the scavenging activity on DPPH·of compound 3a is 5 times than that of resveratrol (IC50=54.76μM) and 6 times than that of the commonly antioxidants 2,6-di-tert-butyl-4-methyl phenol (BHT, IC50= 54.76μM). The IC50 of the remaining nine compounds but compound 1b scavenging on ABTS·+ was less than resveratrol (IC50=15.47μM) and BHT (IC50= 36.98μM), showing that these compounds'scavenging activity were better than that of resveratrol and BHT. Scavenging activity of 2a against ABTS+·is far better than the other nine compounds and its IC50 is 3.68μM. The research shows the antioxidant activity of compounds can be improved through exclusive structural transformation of resveratrol based on the principle of bioisosterism.(Ⅱ) The study of antioxidant's chelation abilities to transition metal ions and DNA plays an guiding role in accurate assessment of the sequestration mechanism of antioxidant mechanisms. Ten compounds'chelation abilities to transition metal ions (Cu2+,Fe2+,Fe3+) and DNA were investigated by UV-vis spectroscopy and fluorescenece spectra. The result shows that ten compounds have good chelating ability with transition metal ions Cu2+, Fe2+, Fe3+, DNA. In the model of UV spectra, Compounds 2a has the best chelation abilities on Cu2+ with its quenching constants 1.22×104M-1; Compounds 2b has the best chelation abilities with Fe2+ and Fe3+, and the quenching constants were 2.1×104M-1,8.67; In the model of fluorescenece spectra, Compounds 3a has the best chelation abilities with Cu2+ and Fe2+, and the quenching constants were 2.36×104 M-1,7.31×104M-1, Compound la has the optimal chelation abilities on DNA with the quenching constants 9.67×103M-1. The study shows that chelation of transition metal ions and DNA chelating are the compounds'antioxidant role and work mechanisms.(III) As coumarin derivatives have important biological activity,17 new coumarin-schiffbase compounds were synthesized based on m-Dihydroxybenzeneas through cyclization, substitution, oxidation, condensation reaction. Compounds'free radical scavenging activities against DPPH·, ABTS+·,-OH,02-·free radical were evaluated. The results show that most of the compounds exhibite good scavenging activities on DPPH·, ABTS+·, OH,02-·free radical. Compound 5f2 shows the strongest scavenging activity on DPPH free radical with it's IC50 at 6.91μM, its activity is better than resveratrol and BHT; Compounds 5g1 shows the strongest scavenging activities on ABTS free radical with it's IC50 at 1.29μM; Compound 5e1 shows the strongest scavenging activity on hydroxyl radical with its IC50 at 34.61μM, its activity is better than ascorbic acid vitamin C (IC50=73.81μM); Compound 5g2 has the best scavenging activity on 02-·with its IC50 at 33.13μM, its activity is better than BHA. The research shows that the introduction of base functional groups to the coumarin skeleton argument may improve the antioxidant activity of compounds.(Ⅳ) The chelation abilities of 17 compounds with Cu2+,Fe2+,Fe3+ and DNA, BSA were studied by fluorescence quenching. The results show that most of the compounds have good chelating ability on Cu2+, Fe2+, Fe3+, DNA, BSA with quenching constants in the range of 102～105M-1. Compound 5c1 shows the best chelating ability on Cu2+ and Fe2+, and the binding constants are 4.46×105M-1 and 3.85×105M-1; Compound 5e3 has good chelating ability on Fe3+, and the quenching constants was 3.94×105M-1; Compound 5d1 has the best chelating ability to DNA with quenching constant 4.68×104M-1; Compound 5b2 has the best chelating ability on BSA with quenching constant 4.34×106M-1. The research shows that the compounds'chelation to transition metal ions,DNA and serum proteins of chelation are the compounds antioxidant role of the mechanism and work mechanisms.In summary,27 compounds were synthesized in this paper. Their structure was characterized. The antioxidant activity of compounds was evaluated, and the functional mechanism of the compounds was shtudied through the investigation of compounds' chelation abilities with transition metal ions, DNA, BSA.