Bioactivity Of Low Molecular Weight Chitosan Derivatives

Based on their excellent physical chemistry properties and pharmaceutical function, chitosan and their derivatives have been applied in the pharmaceutical field and biological materials. In this thesis, we had prepared a serious of low molecular weight chitosan supported metal complexes and study their bioactivity. Firstly, there have reviews with two topics: One focus on the development of studies of active oxygen free radical and antioxidant. Another is about pharmaceutical function and biological activities of chitosan and their derivatives.Secondly, a new system Co²⁺-H₂O₂-bromopyrogallol red (BPR) with the catalyst of thiourea for investigating hydroxyl free radical (·OH) is developed from the traditional assay system. The system produces catalytically hydroxyl free radical by thiourea. According to the interaction of hydroxyl free radical and bromopyrogallol red, the amount of hydroxyl free radical produced in the system can be indirectly assayed through absorbance change at wavelength of 553.5 nm in spectrophotometer. Compared to the result, the method proved to be rapid, simple and stable. It can be used to select antioxidants.The antioxidant activities of Schiff base cobalt complexes of low molecular weight chitosan (CS) were assayed by the catalytic oxidation reaction with BPR and thiourea. The results indicated that CS Schiff base cobalt complexes can scavenge hydroxyl free radical (OH), and CS salicylaldehyde Schiff base cobalt complex is superior to others.Thirdly, low molecular weight chitosan (CS) supported metalloporphyrin complexes (MTAPP-CS,MTPPS₄-CS, M=Cu, Zn, Co) were prepared. These complexes were characterized by ICP and UV/Vis analysis. The interaction between MTAPP-CS and MTPPS₄-CS with DNA was investigated by fluorescent probe technique. The results showed that MTAPP-CS and MTPPS₄-CS can destroy the structure of DNA. The antitumor activities of these complexes were studied by SRB assay. It was found that these complexes show strong antitumor activities. Finally, the CS supported 5-Fluorouracil was prepared by physical adsorption of 5-Fluorouracil into CS. The antitumor activity of this product was evaluated in vitro by using SRB assay. The antitumor activities decreased with increasing of the ratio of CS and 5-Fluorouracil. The results show CS/(5-Fu) (5:1) and CS/ (5-Fu)(10:1) have good antitumor activities, and its IC50 is 31.6μg/mL and 58.8μg/mL respectively. It can be concluded that natural macromolecule / drug composite could lead drugs directly into a tumor or to release the toxicity of small molecule antitumor medicine at the same time. Compared with chemical binding, physical absorbing is simple and effective.