Series Of Flavonoids Synthesis And Biological Activity Evaluation

Flavonoids are a large group of natural products with a wide range of biological activities. Most of them lack enough bioavailability. The bioactivity of this type compound is also not strong enough for the drug development. If the flavonoids are used as lead compound, the structure modification and structure activity relation study will improve the potency of bioactivity and bioavailibility. Optimized structure based on SAR study will have possibility to be found for the drug discovery. Therefore, the design and synthesize of diverse structure of this type compounds are necessary.In this dissertation,29flavonoids were designed and syntheseized based on the modified Baker-Venkataraman's rearrange reaction.7of which have not reported before.5of β-malonyl ketone compounds were syntheseized for the first time. The prepared compounds provided a possibility for the biological activity assay.In order to enhance the solubility in lipophilic solvent and pharmacodynamic effects of flavonoids, four6-benzoyloxyflavone and7-benzoyloxyflavone and their derivatives are prepared by the reaction of6-hydroxyflavone and7-hydroxyflavone with benzoyl chloride in acetone solution in the presenee of potassium carbonate. All of the four compounds are not repeorted so far in the literature. The solubility of these compounds in lipophilic solvent is improved indeed.In order to enhance the water-solublity and pharmacodynamic effects of flavono-ids, the7-(3-chloropropyloxy)-flavone was synthesized by the reaction of7-hydroxyflavone with1-chloro-3-bromine propane. Then norfloxacin was connected to position7in A-ring of flavone by the nucleophilic substitution of7-(3-chloropropyloxy)-flavonewith norfloxacin. The water-solublity of the synthesized compound has been improved greatly.Anti-tumor activities of the synthesized flavonoids and β-malonyl ketone compounds were evaluated against HeLa cells lines in vitro by the standard MTT method. The result showed that compounds25,31,and13b have antiproliferative activities against HeLa cell lines with IC50values of19.4μM,87.9μM and95.5μM respectively。 Antibacterial activities of flavonoids and P-malonyl ketone compounds were studied by the method of filter paper. The results showed that compound25have activity to inhibit P. aeruginosa and E. coli with IC50values of2.5and0.313mg/mL respectively and has no activity to inhibit Staphylococcus aureus. The remaining38compounds have no antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. The compounds1-(2-hydroxy phenyl)-3-(4'-chlorophenyl)-1,3-propanedione and4'-chloro-7-dihydroxyflavone can inhibit swarmming athletic ability of Pseudomonas aeruginosa. While the compound4'-methyl-6-benzoyloxyflavone can improve swarmming athletic ability of Pseudomonas aeruginosa.