Investigation The Interaction Of Several Antitumor Drugs With Proteins By Spectroscopic Methods

Artemisinin, dihydroartemisinin, cantharidin, norcantharidin, neohesperidin and naringin possess biological activities and pharmacology properties. Artemisinin and dihydroartemisinin have outstanding antimalarial activities, and they are regarded as the main anti- malarial drug. Additionally, they also have some functions, such as antitumor and anti-cancer. Cantharidin and norcantharidin has been regarded as an antitumor drug to cure esophageal, hepatoma and gastric. Moreover, norcantharidin has less cytotoxin than cantharidin in various cell lines, so it provides a number of clinical applications. Neohesperidin has a lot of pharmaco logical actions, such as antiproliferative, anti-allergic, antioxidant, antiestrogen, anti-tumor, free radical scavenging activity and protective effects on gastric diseases. However, Naringin has many kinds of efficacy, including antioxidant, antihypercholesterolemic, anti- inflammatory, antihyperglycemic, anti-apoptotic and cardioprotective effects, and it has become a new drug which has many application values. In the paper, the interactions of these antitumor and anti-cancer drugs with proteins have been discussed. It helps to understand the transport in vivo, pharmacological actions information and pharmacokinetic of these drugs, and provide basic theoretical studies for the synthesis of their highly active analogues. The concrete study is as follows:The interactions of dihydroartemisinin(DHA) and artemisinin(ART) with bovine serum albumin(BSA) have been investigated by fluorescence, UV-vis absorption and Fourier transform infrared(FTIR) spectra in simulated physiological conditions. The binding characteristics of DHA/ART with BSA were determined using fluorescence emission and resonance light scattering(RLS) spectra. The quenching mechanism between BSA and DHA/ART is static. The binding constants and binding sites of DHA/ART-BSA systems were calculated at different temperatures. According to F?rster non-radiative energy transfer theory, the binding distance of BSA to DHA/ART was calculated to be 1.54/1.65 nm. The effect of DHA/ART on the secondary structure of BSA was analyzed by UV- vis absorption, synchronous fluorescence and threedimensional fluorescence spectra. In addition, the change of the peak position and intensity has been analyzed by FT-IR spectra in the presence of DHA/ART, a nd we also calculated their corresponding FT-IR spectra data using simulation method. Then the secondary structure content of BSA could be obtained. The major decrease in α-helix and increase in β-sheet and random structure suggested that a partial protein unfolding induced by DHA/ART. Finally, the influence of common ions on the binding constants of BSA-DHA/ART systems was also discussed.The interactions of Cantharidin/Norcantharidin(CTD/NCTD) with two blood proteins(BSA and BHb) have been investigated through the same methods above. The results indicated that the microenvironment of Trp residues on BSA/BHb altered, the peptides strand less extended, and the hydrophobicity increased with the addition of CTD/NCTD. Moreover, we further studied the concentration profiles and the corresponding pure spectra of different components of these four binding system by multivariate curve resolution-alternating least squares(MCR-ALS) technique. The resolved spectra of free CTD/NCTD and BSA/BHb agreed well with their corresponding measured counterparts. The fitting results were obtained by analyzing the corresponding fluorescence and UV-vis data expanded matrices of these four binding system based on MCR-ALS model. We concluded that CTD/NCTD bound to two blood proteins and four complexes(C TD-BSA, NCTD-BSA, CTD-BHb, and NCTD-BHb) were formed. The results of fluorescence quenching showed that the quenching mechanism of two blood proteins with CTD/NCTD is static quenching. The binding constants Kb, the number of binding sites n, the binding distance r and the thermodynamic parameters were calculated. The results of synchronous fluorescence, FT-IR and three-dimensional fluorescence spectra suggested that the conformations of BSA/BHb altered with the addition of C TD/NCTD.The bindings of Neohesperidin/Naringin(NHD/NRG) with BSA/BHb have been studied by several different spectroscopic methods. The results suggested that the quenching mechanism of BSA/BHb with NHD/NRG is static quenching. The number of binding sites n, the binding constants Kb, the thermodynamic parameters(such as, ΔG, ΔH, and ΔS) and the distance r were calculated at various temperatures. The conformations of BSA/BHb altered with the addition of NHD/NRG. In addition, we investigated the influence of common ions on the binding constants of BSA-NHD/N RG and BHb-NHD/NRG systems. In addition, the simultaneous determination of NHD and NRG in Weifuchun tablet samples has been established using partial least squares(PLS).