| Matrine extracted from sophora flavescens and other Chinese herbal plants has many pharmacological effects,such as antipyretic,analgesic,myocardial protection,antiarrhythmic,preventing liver fibrosis,antibacterial and antiviral,etc.it is also a low toxic natural plant insecticide.Matrine,as a representative compound of alkaloids,has broad-spectrum pharmacological and diverse biological effects,and has become a hot research object of natural drugs for pharmacologists and synthetic chemists.However,the low activity of matrine limits the application of matrine.Through chemical synthesis,the structure of matrine was modified,including structure derivation and structure transformation,and its activity was determined and compared.After optimization,the toxicity was reduced,the activity and bioavailability were improved,and the utilization of matrine was more safe and effective.In this paper,two routes were designed based on the principle of drug combination.The first route is to obtain chloroformyl matrine from matrine by weiersmeier reaction,and then react with guanidine hydrochloride to obtain aminopyrimidino matrine.Finally,29 kinds of amido pyrimidino matrine derivatives were obtained by condensation with different substituted aryl formyl chlorides.The second route is to synthesize aminopyrimidino matrine derivatives from matrine under the catalysis of LDA six diphenylpyrimidino matrine derivatives were obtained by the reaction of benzonitrile compounds.The structure of the target compound was characterized and identified.The results of in vitro antitumor activity test showed that JWT-03,JWT-08,JWT-13,JWT-18 and JWT-20 had good inhibitory activity on MCF-7(human breast cancer cells)and He La(human cervical cancer cells),and JWT-02 and JWT-15 had the same inhibitory activity on single cell line as cisplatin in the positive control group,significantly better than matrine. |
