The Design And Synthesis Of Butein Derivatives, And The Study Of Antidepressant Activities

Butein,2′,3,4,4′-four hydroxyl chalcone is a kind of natural polyphenols extractedfrom plants, with antioxidant and anti-inflammatory, inhibiting protein kinase, HIV-1protease etc, and has high application value in life and medicine. Because of its lowcontent in the plant, using the method of chemical synthesis of riveting purple flowersand its derivatives is particularly important. Designed and synthesized in this paper twoseries of Butein derivatives, and research of the antidepressant activity.With natural purple riveting, Butein (2,3′,4,4′-four hydroxyl chalcone as leadcompounds using the split principle in the design of new drugs for structuralmodification, with2,4-dihydroxyacetophenone as the starting material, throughWilliamson reaction, claisen-schmidt condensation reaction, reduction reaction, trackreaction with thin layer chromatography and using silica gel column chromatographypurified compounds, got the first series of Butein derivatives, namely2′-hydroxyl-4′-isopentenoxyl chalcones. And, on this basis, with2′-hydroxyl-4-isopentenoxyl chalcones derivatives as the starting reagents, with weak base sodiumacetate, under the condition of anhydrous ethanol, through Michael reaction and usingcolumn chromatography purified compounds, get the second series of Butein derivatives,namely7-isopentenoxyl-2,3-dihydroflavonoids derivatives. All synthetic compounds byIR,1H-NMR,13C-NMR and MS for structure identification, and use the classicdepression model mice forced swimming test and mouse tail suspension test for the studyof antidepressant activity of the synthetic compounds.Forced swimming pharmacological experiment results showed that the synthesis ofnineteen2′-hydroxyl-4′-isopentenoxyl chalcones, compared with the blank controlgroup (139.00±13.50s), have shown a certain antidepressant activity. Among them,there are six compounds, namely,4b,4c,4e,4f,4h,4k,4m at the dose of10mg/kg,theresult were77.80±12.20s,76.80±13.40s,62.20±10.70s,57.50±11.80s,70.20±10.20s,65.00±12.90s,71.70±11.90s, similar with the positive group fluoxetine(62.50±9.30s),showed the good activity. Three compounds of4i,4l,4n, whose immobility time were36.70±8.50s,41.70±12.40s and12.40±9.20s, compared to positive controlgroup fluoxetine (62.50±9.30s), their immobility time is less than the fluoxetine’s inforced swimming, showed the antidepressant activity better than that of fluoxetine. And,in the tail suspension test in mice, the three compounds (4i,4l,4n) compared with theblank group have significant differences, three compounds showed better antidepressantactivity. To the good acticity compounds4i,4l,4n,we inject in mice in oral, theexperimental results show that the compound4i,4l,4n significant difference comparedwith blank group, showed better antidepressant activity. In addition, automic activities inmice is no obvious change through open field test, it shows that compound4i does notchange the automic activities in mice, thus, it exclude the false positive result ofantidepressant.To the another series of synthesis, fourteen7-isopentenoxyl-2,3-dihydroflavonoi-dsderivatives, the experimental results show that in the forced swimming test in mice,compared with the blank group (90.00±18.01s),8compounds (5b-5e,5g,5h,5j,5k)have significant difference, the immobility time respectively is5b(54.20±18.30s),5c(43.60±19.00s),5d(46.40±24.40s),5e(37.20±4.30s),5g(48.00±16.90s),5h(46.00±18.60s),5j(21.80±16.00s),5k(24.00±9.70s). Among them, the two compounds5jand5k compared to the positive group fluoxetine (62.50±9.30s), have the similarimmobility time， shows the better antidepressant activity. The two good activecompounds5j,5k in mouse tail suspension test, the experimental results show that thesetwo compounds can shorten the immobility time, suggests that these two compoundswith antidepressant activity.Conclusion: based on the Butein as lead compounds, synthesis of a series of Buteinderivatives, and research the antidepressant activity of this series derivatives, preliminaryevaluation for its antidepressant activity. Pharmacological experimental results showsthat compound4i,4l,4n,5j,5k all showed good antidepressant activity, including4i,namely3-bromine-2′-hydroxy-4′-isopentenoxyl chalcones and5j,2-(4-brominephenyl)-7-isopentenoxyl-benzo pyran-4-ketone have the best antidepressant activity.