Synthesis And In Vitro Antitumor Activity Of Matrine/Sophoridine Arylimine Derivatives And Matrine/Sophoridine Quinoline Derivatives

Matrine and sophoridine are two structurally similar alkaloids in the leguminous plants such as sophora flavescens,sophora alopecuroides,and sophora radix leguminous roots,and they are also the main components in fufang kushen injection.Matrine and sophoridine have several pharmacological activities such as anti-inflammatory,anti-viral and anti-tumor.In the study of important monomers in fufang kushen Injection,it was found that the combination of multiple compounds was synergistic and had fewer side effects.However,the activity of individual compounds such as matrine and sophordine were not outstanding.Therefore,it was proposed to increase the anti-tumor activity of matrine and sophoridine by the method of structural modification.In this paper,on the principle of medicine combination,at first matrine and sophoridine as raw materials,was catalyzed by phosphorus oxychloride and combined with a variety of aromatic amines to get 29 types of matrine arylimine derivatives and 29 types of sophoridine imine derivatives.Then,a variety of o-cyanoanilines were combined with matrine and sophoridine as imine intermediate products,and they were again cyclized to matrine and sophoridine under the catalysis of a strong nucleophilic base,lithium diisopropylamide.Finally,8 matrine derivatives and 3 sophoridine derivatives contains quinoline structure was obtained.The structure of the target compounds were characterized and confirmed.In vitro tests showed that A-20,B-20,B-21,B-27,B-28,A-30～A-37 and B-30～B-32 have ideal anti-tumor activity on human hepatoma cells(HepG2)and human cervical cancer cells(HeLa).Worthly,compounds A-34,A-35 and B-31 showed higher cytotoxicity than positive control drug camptothecin.