Preparation And Antioxidant Activity Of Chitosan Derivatives Bearing Quinoline Groups

Chitosan,also known as deacetylated chitin,has the characteristics of renewable,low cost and good biocompatibility.However,the commercial application of chitosan is limited due to its poor water solubility and relatively weak biological activity.The molecular structure of chitosan can be changed by introducing other active groups through chemical modification,so as to improve its biological activity.As the core skeleton of a variety of drugs,quinoline has a variety of biological activities,such as antioxidant,antibacterial,anti-malaria,antiviral and anti-tumor activities.Therefore,the grafting of quinoline groups into chitosan molecules by different chemical reaction methods is an important method to enhance its biological activity.In this paper,a total of 25 chitosan quinolinyl urea derivatives,chitosan quinolinyl amide derivatives and chitosan quinolinyl quaternary ammonium salt derivatives were prepared by various reaction strategies.The structures of chitosan derivatives were characterized by infrared spectroscopy and nuclear magnetic resonance hydrogen spectroscopy.The contents of carbon and nitrogen in the derivatives were determined by elemental analysis and the degrees of substitution of chitosan derivatives bearing quinoline groups were further calculated.In addition,the effects of the introduction of active quinoline group on the bioactivity of chitosan derivatives were studied by antioxidant activity and cytotoxicity tests in vitro.Firstly,aminoquinoline was inserted into chitosan molecules to obtain four kinds of chitosan quinolinyl urea derivatives with 2-methoxyformylated chitosan as intermediate.The antioxidant activity test showed that the introduction of quinoline group effectively improved the free radical scavenging ability of chitosan derivatives.Under the maximum concentration of 1.6 mg/m L,the scavenging efficiency of chitosan quinolinyl urea derivatives on DPPH free radicals,superoxide anion free radicals and hydroxyl free radicals exceeded 50%.Especially the scavenging ability of hydroxyl radical,the clearance rate of derivatives reached more than 95%.Cytotoxicity test results showed that chitosan quinolinyl urea derivatives exhibited no cytotoxicity on L929 cells.Secondly,four O-acetamido quinolinyl chitosan derivatives,four N-acetamido quinolinyl chitosan derivatives and four N,O-acetamido quinolinyl chitosan derivatives were prepared respectively with three carboxymethyl chitosan as intermediates.The antioxidant activity in vitro showed that the free radical scavenging activity of chitosan quinoline amide derivatives was higher than that of chitosan and carboxymethyl chitosan.In addition,the scavenging ability of N,O-acetamido quinolinyl chitosan derivatives was also significantly improved compared with O-acetamido quinolinyl chitosan derivatives and N-acetamido quinolinyl chitosan derivatives,indicating that chemical modification of amino and hydroxyl groups in chitosan molecules was beneficial to improve their biological activity.Moreover,cytotoxicity tests showed that most derivatives were not cytotoxic to L929 cells.Finally,four N,N,N-trimethyl-O-acetamido quinolinyl chitosan quaternary ammonium salt derivatives and five N,N,N-trimethyl-O-chloroacetyl quinolinyl chitosan quaternary ammonium salt derivatives were prepared via N,N,N-trimethyl-O-carboxymethylated chitosan and N,N,N-trimethyl-O-chloroacetyl chitosan.In vitro antioxidant activity tests showed that the scavenging ability of the nine derivatives on free radicals was significantly improved and the scavenging rate was more than 50% at 1.6 mg/m L.Particularly,the reduction capacity of N,N,N-trimethyl-O-chloroacetyl quinolinyl chitosan quaternary ammonium salt derivatives was significantly enhanced compared with other derivatives.Cytotoxicity tests showed that N,N,N-trimethyl-O-chloroacetyl quinolinyl chitosan quaternary ammonium salt derivatives 2a and 2e showed cytotoxicity at high concentrations(cell survival rates of43.08 ± 12.27% and 55.16 ± 7.19% at 1000 μg/m L,respectively).Yet most of the samples showed no cytotoxicity on L929 cells.In summary,the preparation,characterization and bioactivity of chitosan derivatives bearing quinoline groups were studied systematically in this paper.And screened out the N,N,N-trimethyl-O-chloroacetyl quinolinyl chitosan quaternary ammonium salt derivatives with excellent antioxidant activity,which provided a new idea for the application of chitosan.