Screening Method Research Of Artemisinin And Its Derivatives In Vitro

Artemisinin,a sesquiterpeno id endoperoxide,is an active component extracted from the antimalarial herb Qinghao.Because it of high nature targeted antitumoractivity,the study of QHS and its derivatives have attracted more and more attention.Knowledge of binding mechanisms between drugs and plasma protein is very important for us to understand the properties of drugs,such as its pharmacodynamics and pharmacokinetics properties.For its primary pharmacokinetics function isparticipating in absorption,distribution,metabolism and excretion of drug.The binding parameters are helpful in the study of pharmacokinetics and the design ofdosage form,because strong binding interaction can decrease the concentrations offree drugs in plasma,while the weak one can lead to be a short lifetime or poor distribution.Therefore,the binding interactions of drugs and plasma protein in vivo and vitro,considered as a model in protein chemistry to study the binding behavior ofproteins,have been an interesting research field and studied for many years.Three kinds of QHS derivatives have been synthesised,they are 9-OH QHS,DHA and 9-OH DHA.In order to establish the interaction mode between QHS and its derivatives with HB,multiple spectroscopy methods have been used,including UV-vis,steady state/time resolved fluorescence spectroscopy and synchronousfluorescence,circular dichrosim spectroscopy.The conclusion could be of use in:ensuring the influence of interaction to binding site,binding constant,binding force,and the comformational change of biomacromolecule.The experiment results show that QHS and its derivatives have strong binding force with plasma protein,however.there are still visible difference in binding ability and binding constant for its structure difference,the pecking order is,DHA>9-OH DHA>9-OH QHS>QHS.Based on this conclusion,the screening method for antitumor activity of artemisinin compounds in vitro has been preliminary established.In addition,we also use liquid chromatography-mass spectrometry(LC-MS)method to monitor the produce process of the key antitumor C-4 free radicals,which:provides valuable reference for the screening method for artemisinins' antitumor activity in vitro.