The Characterization And Pharmacodynamics Study Of Piperine Derivatives

In this article,two derivatives of piperine are synthesised,hydrogenated derivatives and piperinic acid.Synthesized compounds are characterized by UV,IR,1HNMR,MS spectrum.The efficacy of two derivatives is studied initially.Molecular simulation is used to predict the reactivity of piperine.Major research results are as follows:1.Through hydrogenation catalyzed by Pd/C,piperine hydrogenation derivative was carried out as saturating conjugated double bonds.Purity analysis is carried out by HPLC.Results show that the purity is more than 95%.Successively,derivative was characterized by UV,IR,1H NMR,MS spectrum;Discuss the acid-base stability,light stability,thermal stability.To do further research,study the physical properties(melting point,decomposition temperature,etc.)of derivative by making use of comprehensive thermal analysis.Differences of thermodynamic properties are studied by comparing difference of the DSC and TG curve between before and after the reaction.2.Research on the hydrolysis of piperine amido part.Discussion on influence of different mobile phase ratio,flow velocity,column temperature on peak.Isocratic elution demonstrated:when methyl alcohol(A)and water(C)77:23,flow velocity 0.8 mL/min,column 25?,the peak was best.Piperic acid was characterized by UV,IR,1HNMR.Further,acid-base stability,light stability,thermal stability of it was discussed.3.Inoxidizability of piperic acid was explored with OH radical scavenging capacity measurement,DPPH radical scavenging and super oxygen anion free radical(02-)clearance.OH radical kit measurement showed that:with the concentration increased,inoxidizability of piperinic acid increased,when the concentration reached 0.2 mg/ml,the inhibition rate reached 51.67%;when the concentration continue to increasing,the augment of inoxidizability was not obvious.DPPH radical scavenging test showed that:with the concentration increased,oxidative stability of it was strengthen.When concentration was 0.6 mg/ml,the inhibition rate reached 82.86%;When concentration continued increasing,inhibition rate remained invariable.Super oxygen anion free radical(02-)clear results showed that:with the concentration increased,changes was as above.When the concentration was 1.1 mg/ml,clearance rate reached 66.01%;When the concentration continued to increase to 1.4 mg/ml,clearance rate is not increase with concentration.4.Anticonvulsive effect of piperine and the derivatives are researched.Select KunMing mice,and conduct a seven-day lavage.Experiments indicated piperine and its derivatives show a good performance in anti-convulsion effects,and their anti-convulsion effects are near.Judge initially,the two changes in the structure of the original piperine have not negative effect influence on pharmacodynamics,will not lead to the weakening of efficacy.5.Molecular model of piperine is built by Materials Studio5.5 of Accelrys Corporation.Optimal structure of the model is obtained after three steps optimization.Three steps optimization respectively is molecular mechanics optimization,molecular dynamics optimization,quantum mechanical optimization.Use primary principle to compute piperine charge distribution,optical properties.According to the experiment,the theoretical results are in agreement with the experimental results.Molecular simulations predict reaction active site of piperine.Namely,double bond parts is prone to addition reaction,and amide linkage is easily alkaline hydrolysised.Ether bonds is easily acid hydrolysised to unlock ring.