Design,Synthesis And Study Of Pharmacological Activity Of 2H-benzo[f]-Chromen Chalcone Derivatives

Chalcone,a chemical name of 1,3-diphenylpropenone,is a flavonoid compound.Chalcone and its derivatives show a wide range of biological activities.Based on the previous research work of the research group,a series of 2H-benzo[f]-chromen chalcone derivatives were designed and synthesized,and the antidepressant,anticonvulsant,anti-inflammatory and analgesic activities of the derivatives were studied.Research methods: 19 2H-benzo[f]-chromen chalcone derivatives(2a-2s)were obtained while 2-Hydroxy-1-naphthaldehyde was used as the starting material,thin layer chromatography(TLC)was used to detect experiments.The compounds were purified by recrystallization.All the structures of the synthesized compounds were determined by IR,1H-NMR,13C-NMR and ESI-MS.The antidepressant activity,anticonvulsant activity,neurotoxicity,anti-inflammatory activity and analgesic activity of derivatives were evaluated by the classical anti-depression model "Forced Swimming Test"(FST),the maximal electroshock seizure(MES),rotarod test,the mouse ear swelling test and the acetic acid-induced pain test.Research result:(1)The results of forced swimming test in mice showed that 18 compounds(2a-2l,2n-2s)significantly reduced the immobility time when the dose was 30 mg/kg,showing certain antidepressant activity,especially 3 derivatives(2b,2d,2n)had significant antidepressant activities with the reduction rates of immobility time were 85.05%,75.38% and 67.52%,respectively,which were similar to the antidepressant activity of fluoxetine hydrochloride.(2)The maximum electroconvulsant convulsion test results in mice showed that 11 compounds 2a,2b,2c,2d,2e,2f,2g,2k,2m,2n and 2q showed anticonvulsant activity at the dose of 100mg/kg.8 compounds 2h,2i,2j,2l,2o,2p,2r and 2s showed anticonvulsant activity at the dose of 300mg/kg.All the compounds showed no neurotoxicity in the rotation test at the same dose.(3)Xylene-induced ear swelling test results: 19 2H-benzo[f]-chromen chalcone derivatives 2a-2s showed good anti-inflammatory activity at the dose of 30mg/kg,especially compounds 2g,2q and 2r showed significant anti-inflammatory activity with the inhibition rates were 84.14%,83.12% and 83.58% respectively,and the anti-inflammatory activity was better than indomethacin(82.19%);7 compounds 2a,2b,2e,2j,2l,2n and 2m mice ear swelling inhibition rate were 73.28%,70.13%,74.95%,79.78%,76.25%,74.58% and 79.31% respectively,which were better than the anti-inflammatory activity of ibuprofen(69.02%),but lower than indomethacin.5 compounds 2d,2f,2i,2o and 2p mice ear swelling inhibition rate were 66.05%,67.07%,67.9%,67.16% and 67.07% respectively,which were similar to the anti-inflammatory activity of ibuprofen.(4)The results of acetic acid-induced pain test showed that the analgesic rate of 19 compounds 2a-2s reached more than 50%,and all of them were above 96%,all of which showed strong analgesic activity.9 compounds 2a,2d,2g,2k,2l,2n,2o,2p and 2r had 100% analgesic rate,which was similar to ibuprofen(100%).Main conclusions: Based on the preliminary work,19 2H-benzo[f]-chromen chalcone derivatives were designed and synthesized.The antidepressant activity,anticonvulsant activity,anti-inflammatory activity and analgesic activity were preliminarily evaluated,and the structure-activity relationship was discussed,which provided a basis of theory for a new class of antidepressants with signifcant biological activity and less toxic side effects.