Study On The Synthesis And Biological Activities Of Paeonol Derivatives

Paeonol,as an active ingredient in traditional Chinese medicine of Mudanpi or Xu Changqing,has wide range of pharmacological activities,such as anti-oxidation,anti-allergy,anti-age dementia,anti-tumor,anti-bacterial,anti-inflammatory and so on.Compounds containing 1,2,3-triazole ring are widely used in the fields of medicine,agriculture and food industry.For example,some compounds containing 1,2,3-triazole are HIV-1 protease inhibitors.Lactam-containing 1,2,3-triazole is a highly selective herbicide and benzotriazoles can be used in food packaging.In this thesis,paeonol was modified according to the combination principle by introducing biologically activity oxazinone unit and 1,2,3-triazole ring into the structure of paeonol to obtain paeonol triazole derivatives.In vitro anti-tumor activity of all the target compounds were tested by MTT method.The content of this thesis is divided into three parts as follows:Firstly,paeonol 1,4-benzoxazinone triazole derivatives were synthesized.Paeonol was used as the raw material to undergo nitration,reduction,amidation and cyclization reaction to obtain paeonol compounds containing the 1,4-benzoxazinone.After that,N-alkylation and Huisgen 1,3-dipolar cycloaddition reaction occurred to obtain the 18 target compounds.The synthesized target compounds were characterized by 1H NMR,13 C NMR,ESI MS and IR.Secondly,paeonol triazole derivatives modified at 2-position hydroxyl were synthesized.Paeonol and 3-bromopropyne were used as the raw material to obtain the intermediate paeonyne.After that,N-alkylation and Huisgen 1,3-dipolar cycloaddition reaction occurred to obtain the 15 target compounds.The synthesized target compounds were characterized by 1H NMR,13 C NMR,ESI MS and IR.Finally,in vitro anti-tumor activities of the synthesized compounds were tested.All the synthesized 33 compounds were tested for in vitro anti-tumor activities by MTT method and paeonol was used as the positive control.There were three kinds of tumor cells containing He La cells(human cervical cancer cells),NCI-H1299 cells(human non-small cell lung cancer cells)and 293 T cells(human renal epithelial cells)in the activity test.The test results showed that most of paeonol derivatives containing the 1,4-benzoxazinone and 1,2,3-triazole moieties had good inhibitory rate to NCI-H1299 cells,which has the best inhibition value of IC50 at 27.56 μM.Most of the paeonol 2-position hydroxyl compounds have good inhibitory rate to He La cells,which has the best inhibition value of IC50 at 0.75 μM.Therefore,they provide the direction to the exploration and research in human lung adenocarcinoma treatment drugs and human cervical cancer treatment drugs.