Synthesis And Biological Activity Of 2-methyl-4-phenylquinolin-chalcone Derivatives

The chalcone structure is 1,3-diphenylpropionone.Among them,the acetone structure is considered as an active essential group.The quinoline core is one of the most important and widely used heterocycles in the development of bioactive molecules.Many therapeutic drugs contain a quinoline structure.Based on previous research,we adopted a rational drug design principle and combined two functional groups to obtain a series of new quinoline-chalcone derivatives.Research on antidepressant,anti-inflammatory and analgesic activity.Research methods:In this step,24 new quinoline-chalcone derivatives were designed and synthesized using 2-aminobenzophenone,acetylacetone and various substituted arylaldehydes as raw materials.All target products were identified by IR,¹H-NMR,¹³C-NMR and MS.At the same time,the antidepressant,anti-inflammatory and analgesic activities of the target compounds were studied through mouse forced swimming experiments,mouse ear swelling experiments,and mouse acetate twist experiments.In order to further explore the possible mechanism,the effects of some compounds in this series on the levels of monoamine neurotransmitters and the inhibitory activity of cyclooxygenase were examined.The results showed that:（1）In the study of antidepressant activity,it was found that out of 24 2-methyl-4-phenylquinoline-chalcone derivatives 2a-2x,it was significant at a dose of 30 mg/kg Decreased the duration of forced swimming in mice and showed some antidepressant activity.Compound 2k had the best activity,and its mouse immobility time inhibition rate was 92.0%.In addition,there are 12compounds（2a,2b,2c,2d,2f,2g,2h,2m,2s,2v,2w,2x）with activity comparable to the positive control drug fluoxetine hydrochloride（76.6%）.（2）In the study of anti-inflammatory activity,it was found that among the 242-methyl-4-phenylquinoline-chalcone derivatives 2a-2x,a significant reduction was achieved at a dose of 30 mg/kg.The degree of swelling of the mouse ear shows a certain anti-inflammatory activity.Compound 2c had the best activity,and the mouse ear swelling inhibition rate was 88.3%.In addition,there are 10 compounds（2a,2e,2g,2h,2k,2l,2n,2o,2s,2w）that are as active as the positive control drug indomethacin（73.9%）.（3）In the analgesic activity study,it was found that in 242-methyl-4-phenylquinoline-chalcone derivatives 2a-2x,a significant reduction was achieved at a dose of 30 mg/kg.The number of writhing in mice in writhing acetic acid writhing experiments shows a certain analgesic activity.The analgesic inhibition rates of compounds 2c,2i,2m,and 2q were 99.3%,99.26%,99.3%,and 99.3%,which were comparable to those of the positive control drug indomethacin group（99.3%）.（4）When studying the effects of test compounds on monoamine levels,it was found that compounds 2c,2k,and 2w increased serotonin levels similar to the control drug fluoxetine without changing the levels of dopamine and norepinephrine.At the same time,when studying the in vitro epoxidation inhibitory activity of the test compound,it was found that the test drugs 2c,2k,2w have weaker COX-1 inhibitory activity.At the same time,the analogs 2c,2k,2w showed moderate COX-2 inhibition.Compound 2k had the best activity and was comparable to the control drug celecoxib.Conclusion:24 novel quinoline-chalcone derivatives were designed and synthesized in this paper.Anti-depressant,anti-inflammatory,and analgesic activities of the target compounds were studied through mouse forced swimming experiments,mouse ear swelling experiments,and mouse acetic acid twist experiments,and its possible structure-activity relationship was discussed.The effects of monoamine neurotransmitters and cyclooxygenase inhibitory activity were studied in order to further explore its mechanism of action.