Study On Synthesis And Biological Activity Of Derivatives Of Quercetin And Genistein

Quercetin and genistein of flavonoid compounds have an extensive range of biological activities such as antibacterial, antioxidant, immunity regulation, antitumor, antilipemic, anti-ulcer effect and so on. In this thesis, the recent studies on pharmacological action, chemical modifications and biological activities of them are introduced. Two new derivatives are synthesized by structure modification of the two kinds of substances, and through the activity study on them, highly reactive substances can be obtained, which has great social value and economic benefit. The relating works are as following:1. Synthesis of quercetin derivative and genistein derivative. Two new derivatives are synthesized through the Mannich reaction. Their structures are characterized by MS, and 1H NMR spectral data.2. Detect the inhibition effect of QD and GD on the activity of cancer cell by MTT method, and detect the effect of GD on the apoptosis of MGC-803 cells through morphological observation by Hoechst 33258 staining and agarose gel electrophoresis. The results show that both QD and GD have certain inhibition effect on MGC-803 cells. While the concentration of QD reaches 40μg/mL, the inhibition rate on MGC-803 is 70.5%; the maximum inhibition rate that the GD has towards MGC-803 gastric cancer cell could be 83.3%, and the MGC-803 treated with GD for 48 h shows obvious morphological change of apoptosis and DNA ladder. The GD also has certain inhibition effect on HepG2 cell, and IC50 is 20μg/mL. QD shows no cytotoxicity on the growth of RAW264.7 cells at the concentrations from 2.5 to 48μg/mL3. GD’s bacteriostatic experiment results show that GD has strong antimicrobial activity. GD’s antibacterial effect against grampositive bacteria (Staphylococcus aureus, Bacillus subtili) is stronger than against gram-negative bacteria (Escherichia coli, Pseudomonas aeruginos). GD’s antibacterial activity against Bacillus subtili is the strongest, and the inhibition rate on Bacillus subtili is above 90% at the concentrations from 6.25 to 100μg/mL. But the effect of GD on gram-negative bacteria is not significant.4. Through the research on the antiulcer effect and mechanism of QD and GD on ethanol-induced gastric ulcer rats, it is clear that QD and GD can significantly protect gastric mucosa against gastric injury. The mechanism might lie in increasing the antioxidant properties. Moreover, the QD pretreatment considerably increases the levels of GSH/GSSG, SOD activity, CAT activity, IL-10 and PGE2 level, meanwhile, it decreases MPO activity and IL-6 when compared to the ethanol-treated group. The mechanism might also lie in increasing the antioxidant properties by changing the GSH, SOD and CAT activities, regulating and controlling the in vivo contents of prostaglandin E2 and cytokines (IL-6, IL-10).