Study On Conjugates And Inclusion Complexes Of Artemisinin And Its Derivatives With Cyclodextrins

The function, molecular recognition and self-assembly of cyclodextrin and its derivatives are one of the hot areas of supramolecular chemistry today. Drugs molecules is introduced to supramolecular system as basic blocks, which build structures and special features the assembly of complex, and It is important to direct in drug delivery systems. A series of artemisinin that is lipophilic drug molecules was chosen were chosen for the investigation of their binding behaviors with host cyclodextrin molecules by means of ultraviolet (UV),1D and2D NMR, powder XRD diffraction patterns (XRD) and thermal analysis (TG). A series of new compounds were synthesized with high anti-colon cancer activity and intestinal-targeting property, also the influence mechanism is studied. The major contents of this thesis are as follows:1. Cyclodextrins and its derivatives were synthesized. They are mono(6-O-(p-tolylsulfonyl)-β-cyclodextrin, mono(6-amino-6-deoxy)-β-cyclodextrin, mono(6-ethylene-diamino-6-deoxy)-β-cyclodextrin, mono(6-diethylene-triamino-6-deoxy)-β-cyclodextrin and mono(6-triethylenetetramine-triamino-6-deoxy)-β-cyclodextrin, which structures are charactered by NMR.2. Several kinds of inclusion complexes between the chemical structure of the β-cyclodextrin and drug molecule Artemisia Series have been prepared. The chemistry stoichiometry and binding constant of cyclodextrins with drug molecule were investigated by phase-solubility curves. The complex behaviors and inclusion mode are studied by UV-Vis Spetrophotometric,1H NMR spectroscopy and2D NMR spectroscopy. The results indicate that these complexes significantly improve the water solubility of the drugs.3. The artesunate-cyclodextrin of conjugates were synthesized from modified-β-CD and artesunate. The structure of this conjugate was studied by NMR and MS. The characterization of solid conjugate was studied by means of powder XRD diffraction patterns (XRD) and thermal analysis (TG). The cytotoxicity tests for conjugates have been evaluated in vitro for antiproliferative activity by the MTT cytotoxicity assay. The results obtained indicate that conjugates high anti-colon cancer activity and intestinal-targeting property. Mechanism is discussed as fluorescent cyclodextrin probe.4. Water-soluble and stable performance of chitosan-artemisinin conjugates were synthesized.