Study On Synthesis Flavonoids-amino Acids Schiff Base And Properties Based On Tumor Targeting

Objective The aim of this thesis is to synthesize novel flavonoids-amino acid schiff base compounds and investigate the relations between structures and activities. Their structural characterizations, antitumor activity in vitro and targeting are also carried out.Methods(1) All these flavonoids compounds have been isolated by conventional method and structurally characterized by Elemental analysis, 13 C NMR(13C Nuclear Magnetic Resonance), MS(Mass Spectrum) and IR(Infrared Spectroscopy).(2) The properties of flavonoids-amino acid schiff base compounds have been studied by solubility experiment, melting point determination and pH value stability experiment.(3) Moreover, the study of antitumor activities in vitro were used human breast cancer cell MCF-7 and human gastric carcinoma cells SGC-7901 as experimental model by MTT method.Results(1) Ten new flavonoids-amino acid schiff base compounds have been prepared. Quercetin-Glycine schiff base(I); Luteolin-Glycine schiff base(II); Apigenin-Glycineschiff base(III); Myricetin-Glycine schiff base(IV); Dihydroquercetin-Glycine schiffbase(V); Silybin-Glycine schiffbase(VI); Luteolin-Lysine schiff base(VII); Apigenin-Lysine schiff base(VIII); Dihydroquercetin-Lysine schiff base(IX); Silybin-Lysine schiff base(X).(2) Nolvel flavonoids-amino acid schiff base compounds have been synthesized with remarkable water solubility even though maternal flavonoids have poorly soluble in water. The melting point and thermostability of compounds I, II, VI and VII are better than maternal flavonoids. Compounds III, V, IX and X have very nearly the same melting point with maternal flavonoids. However, the thermostability of compounds IV and VIII are lower than maternal flavonoids due to decomposing. There was no obvious transformation of absorbance in the range of pH 3~8. It is indicated that compounds have preferable stability in acidic and alkaline conditions(3) The results of antitumor activities demonstrated that compounds I~X display higher inhibition ratio to human breast cancer cell MCF-7 and human gastric carcinoma cells SGC-7901 than maternal flavonoids. The anti-MCF-7 IC50 of compounds I, II and V reduced compared with the maternal flavonoids, but the anti-SGC-7901 IC50 are equal to maternal flavonoids. Besides, The anti-SGC-7901 IC50 of compound III and VI compared with the maternal flavonoids are decreased significantly. Anti-MCF-7 targeting index of compounds I, II, V, VII, VIII and X are greater than 1. Meanwhile, anti-SGC-7901 targeting index of compounds III, IV, VI and IX are greater than 1. That is, compounds I, II and V possess human breast cancer cell targeting, while compound III and VI possess human gastric carcinoma cells targeting.Conclusion In this paper, ten nolvel flavonoids-amino acid schiff base compounds have been synthesized by utilizing flavonoids compounds and amino acid due to the remarkable affinity of amino acid for cancer cell. Flavonoid molecules with antitumor activities have been introduced into cancer cell to improve the water solubility, thermostability, pH stability, antitumor activity and tumor targeting. In addition, some of these compounds possess human breast cancer cell targeting and human gastric carcinoma cells targeting.