Research On The Interaction Between Coumarin Anticancer Drugs And Cyclodextrin Or Biomacromolecule

In recent years, chronic diseases such as cardiovascular disease and malignanttumors have been becoming the main killer to the health of human being. It isreported that a number of infectious diseases have been controlled effectively. Butchronic disease is still one of the severe diseases harmful to human health. So theresearch of anti-cancer drugs has attracted the earnest attention of people.Coumarin-based anti-cancer drugs have been reported to have anticancer,antioxidant and anti-HIV effects. However, the poor solubility, low bioavailabilityand poor oral absorption of coumarin compounds have limited their clinicalapplication. The inclusion technology of cyclodextrin can obviously improve thesolubility of drugs and reduce their side effects on the body. The curative effects ofanticancer drugs are different in different aqueous medium, so the researches on theinteractions between drug molecules and cyclodextrin or biomacromolecule insimulated body fluid using isothermal titration calorimetry combined withspectroscopy methods are important. The investigation of them will provide newideas and theoretical basis for the development of more effective drugs and drugcarriers.On the basis of literature research combined with our laboratory, theinteractions of coumarin anticancer drugs with cyclodextrin or protein in aqueoussolutions were studied using isothermal titration calorimetry, Uv-visspectrophotometry, fluorescence spectra analysis, circular dichroism spectroscopyand nuclear magnetic resonance spectroscopy. Studies on the interactions ofcoumarin anticancer drugs in alcohol+water solutions with different concentrationwere investigated with the methods of density, viscosity and refractionmeasurements. Based on the experimental data, we discussed the weak interactionsof molecules. As a part of the project supported by National Natural ScienceFoundation (No.21103079), the present work mainly composed of four parts:In the first part: Interactions of coumarin,6-methylcoumarin, and 7-hydroxycoumarin with hydroxypropyl-β-cyclodextrin in water and phosphatebuffer solution were analysed with phase solubility method from298.15K to313.15K. The thermodynamic parameters including stability constant, changes ofenthalpy, entropy and Gibbs free energy were helpful to understand the interactionmechanism of drug molecules in different solvents.In the second part: The host-guest interactions of7-hydroxy-4-methylcoumarinwith sulfobutylether-β-cyclodextrin were investigated in phosphate buffer solution atdifferent pHs with spectroscopy methods. The interaction mechanism was studied onthe basis of stability constant, changes of enthalpy, entropy and Gibbs free energy.In the third part: Study on the interactions of esculin with bovine serum albuminin Tris buffer solution at different pHs were investigated with isothermal titrationcalorimetry and spectroscopy methods. The thermodynamic parameters includingstability constant, the number of binding sites, changes of enthalpy, entropy andGibbs free energy could provide important information for clarifying the biologicaleffects of esculin in living body.In the fourth part: The experimental values of volumetric, viscometric andrefractive index of7-hydroxycoumarin and7-hydroxy-4-methylcoumarin inethanol/1-propanol+water mixtures were investigated from293.15K to313.15K.The results were discussed in terms of weak interactions of the diluted componentwith other species.