Synthesis And Antibacterial Bioactivity Of Curcumin Ferulate Derivatives

Ferulic acid,as one of the abundant phenolic acids in the plant kingdom,has good antioxidant and antibacterial effects.However,its poor lipid solubility,unstable physical and chemical properties and difficult absorption by human gastrointestinal tract easily occur in the utilization process,which seriously limit its development.It was found that ferulate derivatives have better biological activity than ferulic acid,and can significantly solve the problems that encountered in the utilization of ferulic acid.In order to solve the problems of ferulic acid in the utilization and expand its application scope,this thesis used natural ferulic acid as the lead compound,and synthesized curcumin derivatives of ferulic acid through the DCC/DMAP esterification reaction system.The structure of the synthesized curcumin derivatives was characterized by FT-IR,¹H NMR and HRMS,and their physicochemical properties,antioxidant activity Bacteriostatic activity and other biological activities were analyzed;At the same time,the biological activity of the prepared curcumin ferulate derivative nanoparticles also was studied.The main research results are as follows:（1）The ferulate derivatives（FA-CUR）was synthesized by using the DCC/DMAP reaction system,and the structures of the resulting ferulate derivatives were characterized by UV,FT-IR,¹H NMR and HRMS.（2）The antioxidant activity of FA-CUR was studied through DPPH and ABTS⁺free radical scavenging activity tests.The results showed that the free radical scavenging rate of DPPH was significantly higher than that of ferulic acid at the same molar concentration,and it was found that the ABTS⁺free radical scavenging rate of FA-CUR was significantly higher than that of curcumin.It indicates that the antioxidant ability of FA-CUR was enhanced comparing to the raw material ferulic acid.Meanwhile,we tested the antibacterial activity of FA-CUR against Escherich coli,Streptococcus suis,Shewanella putrefaciens,Bacillus cereus,Aeromonas versoni,Delft acidovorans,Pseudomonas fulva.The results shown that the in vitro antibacterial effect of FA-CUR was enhanced with increasing drug concentration and presented in dose-dependent manner.Moreover,it is found that FA-CUR has certain antibacterial effect on the nine selected bacteria,and the in vitro against Bacillus cereus activity of FA-CUR was stronger than for several other bacterial species,and the weakest was Delftia acidovorans.Therefore,it suggests that FA-CUR has a broad spectrum of in vitro antibacterial activity.（3）The antibacterial effect of four cytokines,namely,interleukin,Caspase,tumor necrosis factor and interferon,on Bacillus cereus was studied by preventive administration of FA-CUR.The antioxidant indicators from infected-serum with channel catfish were measured by using a kit.The results showed that after preventive administration of FA-CUR,the expression level of inflammatory factor（IL-4r,IL-6,Caspase-3,Caspase-8,Caspase-9,TNF-α,IFN-γ）m RNA in the model control group was significantly higher than that of the experimental group.It indicated that after preventive administration of FA-CUR,fish can enhance their antibacterial ability by inhibiting the expression of inflammatory factors.The levels of antioxidant enzymes T-AOC and SOD in the fish serum of the model control group and the negative control group are significantly higher than those of the experimental group.It indicated that the antioxidant stress activity can be improved in the fish serum after preventive administration of fish,and then achieve a certain degree of antibacterial effect.In conclusion,The synthesized FA-CUR in this experiment has a certain in vivo preventive effect on Bacillus cereus infection and has the potential to develop into antioxidant and antibacterial drugs.（4）CaCO₃@FA-CUR nanoparticles were prepared,and then we structurally characterized CaCO₃@FA-CUR structure and determine the antioxidant activity,p H responsiveness and antibacterial activity of CaCO₃@FA-CUR nanoparticles.The results show that at p H 5.5,the release rate of FA-CUR in CaCO₃@FA-CUR nanoparticles is faster than that at p H 7.4,and it is found that the ability of CaCO₃@FA-CUR nanoparticles to clear ABTS⁺and DPPH is stronger than CaCO₃nanoparticles at the same concentration;It has certain inhibitory effect against foodborne pathogenic bacteria Aspergillus Niger,Escherichia coli,Staphylococcus aureus and Rhizopus,and its inhibitory activity against Aspergillus Niger and Escherichia coli increased by40.5%and 54.6%,respectively,compared with the original CaCO₃nanoparticles.The result showed that the prepared CaCO₃@FA-CUR nanoparticles is a natural antimicrobial food additive with good antioxidant effects.