Synthesis And Pharmacological Activity Of 3-naphthyl-1-substituted Phenyl-2-propylene-1-ketone Derivatives

The active ingredients of plant origin have the advantages of low biotoxicity,strong selectivity of action sites and good fitness in organism.It is the most important source of human discovery and extraction of active ingredients and applied to the field of new drug discovery.The flavonoid compounds(flavonoid compounds and flxdyonol,including biflavone,isoflavone,aurone,and anthocyanin etc.)as active substances are widely distributed in nature,such as leguminosae,rutaceae,hypericaceae,euphorbiaceae,polygonaceae etc.New biological activities of Flavonoids including antibacterial,antioxidant,anticancer,antidepression,anticonvulsion,antiviral and anti-inflammatory were found by scientists and reported”,and the discovery of new mechanism,activity binding sites biological characteristics of compounds and low toxicity have also been widespread concern by scientists.To find antidepressant compounds in our group's study,we found that 2?-hydroxy-4?-isopentenyloxy derivatives can significantly reduce the duration time in mice within depression model in a dose of 10 mg/kg(The Forced Swimming Test and The Tail Suspension Test),that showed certain antidepressant activity.In order to find compound which have low toxic effect and strong activity,we used3-naphthyl-1-phenyl-2-propylene-1-ketone derivatives as the lead compound,using the principle of isosterism to design for drug,after claisen condensation,designed a series of3-naphthyl-1-substituted phenyl-2-propylene-1-ketone derivatives,and use the classic antidepression model to study the synthesized compounds antidepressant activity.In addition,according to the literature,antidepressant mechanisms are also associated with the occurrence of inflammation and pain in the body,and inflammation and pain can induce depression.Based on this idea,we studied synthesized compounds anti-inflammatory and analgesic activity in which synthesized compounds can induce the risk factors and can induce depression owing inflammation and pain,further proof that compounds with antidepressant activity also has biological activity against inflammation and pain.It provides ideas and inspirations for the research of flavonoid compound antidepressant activity and mechanism,and provides experimental theoretical basis for finding new leading compound and rationally designing anti-depression-inflammatory-pain related diseases.Research methods:we use 1-naphthaldehyde to be the starting material,through claisen condensation to get 21 3-naphthyl-1-substitutedphenyl-2-propylene-1-ketone derivatives,and using thin layer chromatography to track reaction process,use silica gel chromatography technology to purification and purification 3-naphthyl-1-substituted phenyl-2-propylene-1-ketone derivatives structure was determined by IR,1H-NMR,13C-NMR,and mass spectrometry.The antidepressant activity of 3-naphthyl-1-substituted phenyl-2-propylene-1-ketone derivatives was studied by using FST and TST.The analgesic activity was evaluated by acetic acid.The ear swelling method was used to evaluate the anti-inflammatory activity of mice.Research result:(1)The antidepressant activity of 3-naphthyl-1-substitutedphenyl-2-propylene-1-ketone derivatives(a-u)research in mice was evaluated by the classic against depression model “Forced Swimming Text and Tail Suspension Text”.The experimental results showed that the leader compound II immobility time at the dose level of 30 mg/kg is99.3±15.1**(s),20 3-naphthyl-1-substituted phenyl-2-propylene-1-ketone derivatives(a-m,o-u)exhibited antidepressant activity(30 mg/kg).(2)The anti-depressive activity of three 3-naphthyl-1-substitutedphenyl-2-propylene-1-ketone derivatives(o,t,u)was further verified by the TST in mice.The results showed that compounds showed antidepressant activity at the dose of 30 mg/kg after administration for 30 min by intraperitoneal injection,both derivatives can reduced the duration of the immobility time significantly at dose of 30 mg/kg.Structure activity relationship: the anti-depressant activity rank by the substituent group on the acetophenone:4-N(CH3)2>3,4-N(OCH3)2>3,4-N(CH3)2,and compound u showed the best antidepressantlike activity(30 mg/kg)in the TST.(3)The analgesic and anti-inflammatory activities of mice were evaluated by the mouse ear swelling text and the acetic acid-induced pain text for the 21 well-identified 3-naphthyl-1-substitutedphenyl-2-propylene-1-ketone derivatives compounds(a-u):Experimental results showed significant anti-inflammatory and analgesic activity(30mg/kg),and compound m had the best analgesic-like activity(30 mg/kg),compound f showed the best anti-inflammatory-like activity(30 mg/kg).Main conclusions: In this paper,we synthesized a series of 3-naphthyl-1-substituted phenyl-2-propylene-1-ketone derivatives by introducing different substituted acetophenonegroups evaluated their antidepressant,analgesic and anti-inflammatory activity,20 compounds were able to significantly reduced the immobility time of mice(30 mg/kg),showed excellent antidepressant activity.Explored its structure-activity relationship and provides the possibility of further study in new and highly effective antidepressants.