Study On The Interaction Of Artemisinin-like Drugs And Their Supramolecular Systems With BSA

Artemisinin(ART)is a kind of a half times the terpene lactone compound,its derivatives mainly includes double hydrogen artemisinin(DHA),artesunate,artemether(ATM)and artemisia ether.They were now mainly used in the clinical treatment of malaria.Artemisinin not only have antimalarial effect,but also have the function of pregnant resistance,anti fibrosis,resistance to schistosomiasis,toxoplasma resistance,resistance to a variety of action such as arrhythmia and tumor cell toxicity.Artemisinin is a kind of developmental drugs.At the same time,these drugs as a treatment for malaria in the international market are in short supply,so the artemisinin drugs research and development work is of great significance.But the artemisinin has the disadvantages of water-soluble poor,low bioavailability,and easy being broken down by oxidation and deterioration in reducing agents,light or oxygen.Cyclodextrin can be divided into natural cyclodextrins,single modified cyclodextrins and bridging cyclodextrins.Cyclodextrin is a kind of circular low glucose.Using cyclodextrin and its derivatives(CDs)special structure and unique amphiphilic to improve the properties of drug solubilization and the study of supramolecular chemistry has became a research hotspot.At the same time,in recent years the research of drug molecules interact with proteins has became one of hot point in the field of chemistry and life science.In this article,several supramolecular systems were constructed with three kinds of bridging cyclodextrins and three kinds of artemisinin drugs.The supramolecular systems had been characterized.And then the knot patterns were speculated.Moreover,fluorescence spectrometry was used to study the interaction between supramolecular system and bovine serum albumin(BSA).The major reseach works of this thesis are as follows:1.Three series of ethylene glycol bridging beta cyclodextrin EG-bis-?-CD,DEG-bis-?-CD,TG-bis-?-CD(host 1-3)was synthesized.Supramolecular systems of the guest Artemisinin(ART,guest 1)with three kinds of bridging cyclodextrins had been prepared and characterized by means of ~1H NMR,XRD,SEM and IR.Three possible binding modes of bis(CD)s with artemisinin were analyzed by 2D ROESY.Saturated water solution method experiments showed that after the formation of supramolecular system,artemisinin water soluble increased 0.15 mg/L,0.07 mg/L,0.66 mg/L,respectively.Studied on the interaction mechanism between EG-?-CD/ART supramolecular system and BSA by fluorescence spectrometry.The results showed that a strong fluorescence quenching was observed and the quenching mechanism was considered as static quenching.Hydrogen bonding and van der Waals force as the main driving force to form 1:1 compounds.Meanwhile,the addition of supramolecular system led to the conformation of BSA changed significantly.2.Supramolecular systems of the guest artemether(ATM,guest 2)with three kinds of bridging cyclodextrins had been prepared and characterized by means of ~1H NMR,XRD,SEM and IR.Three possible binding modes of bridging cyclodextrins with artemether were analyzed by 2D ROESY.Water soluble experiments showed that after artemether was packaged by bridging cyclodextrins,the guest of water soluble increased 7.3,7.8,6.1 times,respectively.The interaction mechanism between supramolecular system TG-?-CD/ATM and BSA was investigated by fluorescence spectrometry.The results showed that TG-?-CD/ATM could strongly quench the intrinsic fluorescence of BSA by static quenching.The combined process of Hydrogen bonding and van der Waals forces as the main driving force to form the1:1 compounds.Because of the addition of supramolecular system has influenced on the conformation of BSA.3.Supramolecular systems of the guest Double hydrogen artemisinin(DHA,guest 3)with three kinds of bis(CD)s had been prepared and characterized by means of ~1H NMR,XRD,SEM and IR.Three possible binding modes of bis(CD)s with DHA were analyzed by 2D ROESY.Water soluble experiments showed that after DHA was packaged by bridging cyclodextrins,the guest of water soluble increased1.1,2.2,4.3 times,respectively.The interaction mechanism between supramolecular system EG-?-CD/DHA and BSA was investigated by fluorescence spectrometry.The results showed that EG-?-CD/DHA and BSA could strongly quench the intrinsic fluorescence of BSA by static quenching.The combined process of Hydrogen bonding and van der Waals forces as the main driving force to form the 1:1compounds.Because of the addition of supramolecular system has influenced on the conformation of BSA.4.The interaction mechanism between artemisinin drugs and BSA was investigated by fluorescence spectrometry.Compared with supramolecular system/BSA interaction,Binding constants of drugs/BSA decreased.At the same time,BSA conformation had changed and Binding numbers of DHA/BSA had decreased because of the existanse of briging?-CDs.For a while,it had no effection with interaction of dugs/BSA.