Preparation And Biological Activity Study Of 4-Hydroxyisophthalic Acid Derivatives

World problem-Tumor treatment is a serious challenge in pharmaceutical research.The most important cause of cell canceration is cell signaling pathway disorders caused by cell proliferation,so the research of antitumor drugs is mainly aimed at several key targets in the occurrence and development of cancer cells.It has been shown that that salicylamide compounds have good antitumor effect because the intramolecular hydrogen bonds form a six membered ring configuration,this space configuration is similar to the tinib drugs main parent nuclear 4-aromatic amino quinazoline,which has the same effect as tyrosine kinase inhibitors produce.In order to enhance tumor resistance salicylamide compounds,we use the combination principle and target drug design principle to transform the structure of the corresponding salicylamide.In this thesis,we use 4-hydroxyisophthalic acid as raw material to synthetise twenty two 4-hydroxy-5-bromineisophthalic carboxamides.Intermediates and target compounds are determined by 1H NMR,IR.In order to screen out the compounds with good antitumor activity,the antitumor activity of the synthesized compounds was tested by MTT method,with cisplatin and oxaliplatin as the positive control drug and with MGC-803 human low differentiated gastric cancer cells,SGC-7901 human moderately differentiated gastric cancer cells and MDA-MB-231 human breast cancer cells as target cells,which found that under the same conditions antitumor activity of part of 4-hydroxy-5-bromineisophthalic carboxamides is better than cisplatin and oxaliplatin.The best inhibitory effect on MDA-MB-231 human breast cancer cells and MGC-803 human low differentiated gastric cancer cell isN1,N3-bis(3,4-bis chlorophenyl)-4-hydroxy-5-bromineisophthalamide;The best inhibitory effect on SGC-7901 human moderate differentiation gastric cancer cell is N1,N3-bis(4-iodinephenyl)-4 hydroxy-5-bromineisophthalamide.The apoptosis rate was determined by Annexin V-APC/7AAD staining method through flow cytometry.The 5-bromo-4-hydroxyisophthalamide comp-unds were used to inhibit the growth of cancer cells which the mechanism may be these compounds can induce cancer cell apoptosis.