Synthesis And Antitumor Activity Of Lycorine Derivatives Were Designed Based On The Principle Of Combination

In recent years,the incidence of malignant tumors in China is on the rise.According to the data of the World Health Organization,36%of the new cancer patients every year are Chinese.Therefore,it is of great importance to study new anti-tumor drugs and improve their anti-tumor activity.Lycorine,derived from the bulb of Lycorine,is a kind of natural alkaloid with anti-tumor activity.It is active at very low concentration and has a good inhibitory effect on a variety of tumor cells.In order to enhance the anti-tumor activity of lycorine and reduce its toxicity,the C1 and C2 hydroxyl groups of lycorine were modified and the obtained derivatives were tested for antitumor activity in vitro in order to obtain better antitumor derivatives.At present,lycorine in the market is in the form of lycorine hydrochloride,and hydrochloric acid should be removed to modify the structure of lycorine.In this paper,we found the simple synthesis route of lycorine derivatives.Through the condensation reaction of lycorine hydrochloride with cinnamic acid,indole,pyridine compounds,seven lialline derivatives were obtained.In addition,human liver cancer cell lines He PG-2,human breast cancer cell line MCF-7,and human gastric cancer cell line SGC-7901 were selected for MTT test（the drug concentration was 0.08mmol/L,0.16mmol/L,0.32mmol/L,0.64mmol/L,and1.28mmol/L）.The results showed that the 7 lycorine derivatives had good inhibitory effects on the three tumor cells.The inhibitory rate of indoles compound e on human gastric cancer cell SGC-7901 was the highest,with an IC₅₀value of 0.15mmol/L.The inhibitory rate of pyrrole compound g on MCF-7 of human breast cancer cells was 67.09%with IC₅₀value of0.23mmol/L.The inhibitory rate of cinnamic acid compound a on He PG-2 cells was 68.29%,and the IC₅₀value was 0.16mmol/L.The inhibitory rate and IC₅₀value of the three compounds corresponding to the three cells were almost the same as that of lycorine hydrochloride,but the inhibitory rate of compounds e and g on SGC-7901 was higher than that of lycorine hydrochloride at high concentration.At low concentration,the inhibition rate of Lycorine derivatives a,d and e was higher than that of lycorine derivatives with similar structure that protected the C1 hydroxyl group.This paper is divided into three parts.The first part briefly describes the origin,structure modification and pharmacological action of lycorine.The second part is the experimental content of the synthesis of seven lycorine derivatives.In the third part,the antitumor activity of lycorine derivatives on three kinds of cancer cells was studied.