Synthesis And Antidepressant And Anticonvulsant Activity Of Chromen-Chalcone Derivatives

Chalcone is a compound widely found in many medicinal plants and a kind of 1,3-diphenylpropenone as the core.It is mainly distributed in plants such as Compositae,Leguminosae,and Chicory.Natural chalcone and its synthetic analogs exhibit a wide range of biological activities such as anti-tumor,anti-cancer,anti-oxidation,anti-thrombotic,anti-inflammatory,anti-depressant,anticonvulsant and anti-tuberculosis activities.In recent years,scientific research has deepened and has become a research hotspot on chalcone and its derivatives.Several chalcone compounds isolated from different plants typically exhibit one or more pharmacological activities.Based on the previous research work of the research group,19 chromen-chalcone compounds were designed and synthesized,and they were studied for antidepressant,anticonvulsant,anti-inflammatory and analgesic activities,and analyzed QSAR.Research methods: Salicylaldehyde was used as the starting material,Aldol addition and elimination reactions were carried out with different substituted acetophenones.The progress of the detection was traced by thin layer chromatography,and 19 chalcone compounds were purified by recrystallization.The structure and purity were determined by IR,1H-NMR,13C-NMR and high resolution mass spectrometry.Anti-depressant activity of chalcone derivatives was studied using the classic anti-depression model "forced swimming test"(FST);the derivatives were subjected to maximal electroshock seizure(MES)using the maximal electroshock seizure anticonvulsant activity evaluation;the neurotoxicity of the derivative was tested by the rotation method;the analgesic and anti-inflammatory activities were evaluated by the acetic acid-induced pain method and the mouse ear swelling model.(1)The results of forced swimming test(FST)in mice showed that,in addition to compound 2e,18 compounds at 10 mg/kg could significantly reduce the immobility time of forced swimming,showing a certain anti-depressant activity,4 Compounds(2a,2c,2h and 2k)showed relatively strong antidepressant activity,and the inhibition time of forced swimming in mice was 69.6 %,78.1 %,71.3% and 71.2 % respectively.(2)Evaluation of anticonvulsant activity by using the maximum electroconvulsive test for 19 chalcone compounds(2a-2s): The results of the experiment showed that the 7 compounds(2a,2b,2c,2h,2l,2r and 2s)were able to combat the convulsion and they caused by maximal electroconvulsive at a dose of 30 mg/kg,showing a certain anticonvulsant activity.12 compounds(2d,2e,2f,2g,2i,2j,2k,2m,2n,2o,2p and 2q)were able to combat convulsions and they caused by maximal electroconvulsive at doses of 100 mg/kg,showing some resistance Convulsion activity.In the spin test,no neurotoxicity was shown at the same dose.(3)In the analgesic experiment,9 of the 19 chalcone compounds: 2c,2f,2g,2i-2m and 2q at an dose of 30 mg/kg,the analgesic rate is over 90%,with significant analgesic activity;3 compounds: 2h,2o and 2p at 30 mg / kg dose of analgesia rate of more than 80%,with good analgesic activity;4 compounds: 2a,2b,2d and 2n have analgesic activity of more than 50% at the dose of 30mg/kg,showing a certain analgesic activity;the other compounds have an analgesic rate of less than 50% at a dose of 30 mg/kg,no significant difference compared with the control group and no analgesic activity was shown.(4)The anti-inflammatory activity of 19 chalcone derivatives induced by xylene-induced mouse ear swelling was evaluated.The results showed that 18 compounds: 2a-2k and 2m-2s were administered at a dose of 30mg/kg.Its inhibition rate on mouse ear swelling can reach more than 50%,showing certain anti-inflammatory activity;Compounds(2b,2g,2i,2k,2m,2n,2q and 2r)are administered at a dose of 30 mg/kg.The ear swelling inhibition rates were 84.7%,83.1%,77.9%,87.2%,90.9%,77.0%,78.1 and 88.8%,respectively,with significant anti-inflammatory activity;The compound(21)inhibition rate of swelling was less than 50% and no significant difference compared with the control group,and no anti-inflammatory activity was shown at the 30 mg/kg dose.Main conclusions: Based on the preliminary work,19 chromen-chalcone compounds were designed and synthesized,and their derivatives were studied by forced swimming test,maximal electroconvulsive test,ear swelling and acetic acid induced writhing activity.The antidepressant activity,anticonvulsant activity,anti-inflammatory and analgesic activities of the derivatives were evaluated,and the possible structure-activity relationship of the compounds was investigated.This study provides a new structural and experimental theoretical basis for the search of antidepressants with high activity and low toxic side effects.