Synthesis And Antitumor Activity Of Matrine D-ring Modified Derivatives

Matrine is a special alkaloid belonging to the quinolizidine alkaloid.A large number of studies have shown that matrine has a variety of pharmacological effects,and has developed a variety of preparations,achieved good results.However,due to its low bioavailability,poor chemical stability,and some toxic side effects,there are limitations on its extensive use.Therefore,we hope to structurally modify and modify it by chemical synthesis in order to obtain matrine derivatives with excellent antitumor activity.In this paper,the research on the structural modification and anti-tumor activity of matrine in recent years was summarized,and on this basis,two routes were designed to transform the structure of matrine.The route includes the expansion and shrinkage of the D-ring,and the construction of thiazole heterocycles after D ring opening.The construction of thiazole heterocycles is based on the drug combination principles,which is realized by introducing of the a-carbonyl diazo in the side chain for the first time and cyclizing with thiourea.The introduction of this group provides more possibilities for the modification of matrine and provides a direction for the future modification of matrine.A total of 27 matrine derivatives were synthesized and studied for their anti-tumor activity in vitro.The results showed that most of the compounds were more active than matrine,and C4 and C5 showed a similar cytotoxicity to the positive control drug camptothecin.