Supramolecular System Construction Of Polyamine Modified Cyclodextrin With Tripterygium Wilfordii And Its Interaction With BSA

Celastrol(CSL)and triptolide(TPL)and Triptonide(Tri)belong to Celastraceae.It is the main active ingredient of Tripterygium wilfordii.The research shows that it has antioxidant,anti-rheumatoid,anti-senile dementia and so on.At present,it has become a research hotspot in the fields of cancer,tumor and brain.However,it has poor water solubility,low bioavailability and toxicity,which limits its further development and application.The special structure of ?-CD polyamine modified and two amphiphilic,inclusion and drug molecules,N atoms can form hydrogen bonds with drug molecules,increase the recognition site of the object,improve the bonding ability,can significantly improve the water solubility of the drug molecules,the drug has a better application prospect.In this paper,4 kinds of polyamine modified ?-CDs were synthesized,and 12 kinds of supramolecular systems were prepared.We speculate on possible inclusion patterns.The interaction of 12 supramolecular systems with BSA was studied by UV absorption and fluorescence spectroscopy.The antitumor activities of H1/CSL and CSL were investigated,and the mechanism of H2/CSL supramolecular system and the interaction between CSL and BSA was further studied by theoretical calculation.The main work of this paper is as follows:1.In this paper,4 kinds of polyamine modified ?-CDs(H1-4)were synthesized and characterized by 1H NMR,MS,IR and so on.2.12 kinds of supramolecular systems of H1-4 and Tripterygium wilfordii active compounds were characterized by 1H NMR,XRD and IR.According to the 2D ROESY spectra,the possible inclusion patterns of H1-4 and Tripterygium wilfordii were speculated.UV spectra indicated that between H1-4 and triptolide compounds were formed supramolecular system of type 1:1,the sequence of stability constants between subject and object as KH4/CSL>KH2/CSL>KH3/CSL>KH1/CSL,KH4/TPL>KH2/TPL>KH3/TPL>KH1/TPL,KH4/Tri>KH2/Tri>KH3/Tri>KH1/Tri.Water solubility experiments showed that H1-4 and CSL,TPL,Tri formation of supramolecularsystem,the water solubility of CSL,TPL,increased 63.5,57.6,and 137.3 times,respectively.3.The interation between 12 kinds of supramolecular interaction system and BSA is studied by The UV and fluorescence spectra,and the resuit showed that the supramolecular system with BSA produced a static quenching,and the 1:1 complex formation,combined with the process of hydrogen bonds and van Edward force.The results of synchronous fluorescence spectra showed that the addition of supramolecular system had an effect on the structure of BSA tyrosine residues,but had no effect on the residues of tryptophan residues.The binding distance r is less than 7 nm,which indicates that another reason for the quenching of BSA fluorescence is dipole dipole nonradiative energy transfer.4.To study the in vitro antitumor activity of H1/CSL supramolecular system and five kinds of hepatocellular carcinoma SMMC-7721,colon cancer SW480,lung cancer A-549,leukemia HL-60,breast cancer MCF-7 cells and their toxicity to human normal lung epithelial cells(BEAS-2B).The results showed that the antitumor activity of CSL and H1/CSL supramolecular system on five cells was higher than that of cisplatin.CSL and H1/CSL compounds had certain toxicity to human normal lung epithelial cells BEAS-2B,but the toxicity of H1/CSL was reduced after the formation of supramolecular system.5.Molecular docking and molecular dynamics simulation were used to study the interaction mechanism between H2/CSL and CSL/BSA.The results show that the simulation results agree with the experimental results.