Synthesis Of Benzopyranone-modified Naphthalimide Derivatives And Evaluation Of Antitumor Activity

Malignant tumors are one of the major diseases that cause human death.According to statistics from the World Health Organization,the incidence of cancer is still rising.Therefore,it is urgent for humans to develop highly effective and low-toxic anti-tumor drugs.In recent years,naphthalimides and naphthylactams have attracted attention because of their diverse physiological activities,and Its anti-tumor activity has been greatly developed.Benzo-a-pyrone(coumarin)and benzo-y-pyrone(chromone)are two important class of chromenone compounds,and the natural active products of coumarin and chromone are resistant Antitumor,anti-oxidant,anti-inflammatory,anti-cardiovascular disease and other biological activities,and low toxicity.Based on the years of research on naphthalimide and chromone compounds in this group,this paper based on principles of drug combination design,Coumarin and chromone modification of naphthalimide and naphtolactam respectively,and then through the alkali Sequential coupling of the side chains to construct a target compound library of structural diversity,and a total of 32 benzopyranone-naphthylamide derivatives of seven series were obtained and confirmed by 1HNMR,13CNMR,MS,and elemental analysis.Both are new compounds that have not been reported.Our group has been studying the naphthalimide and flavonoids for many years,and designed and synthesized a flavonoid-naphthalimide-polyamine conjugate with good anti-tumor activity.Based on the previous work of the research group,this paper uses coumarin and chromone as raw materials to modify the active sites on the naphthalene ring of naphthalene amide derivatives,resulting in five series of benzopyrone-naphthalenes that have not been reported.Amide derivatives were confirmed by 1H NMR,13C NMR,MS,and elemental analysis.MTT assay was used to evaluate the in vitro antitumor activity of the above synthesized target compounds.Compounds were tested against seven tumor cell lines(human hepatoma cells HepG2,human cervical cancer cells HeLa,human hepatoma cells SMMC-7721,and human breast cancer cells MCF-7,human colon cancer cell HCT-116,human colon cancer cell HT-29,mouse colon cancer cell CT-26 and a normal hepatocyte HL-7702).The results showed that among the derivatives derived from coumarin-modified naphtolactams,E4 and E5 exhibited better biological activity than other derivatives,of which E5 had weaker inhibitory effects on normal hepatocytes,but on many tumors.The cell lines have strong inhibitory effects,so E5 has better selectivity.To change its structure-activity relationship,it is hoped that compounds with low toxicity to normal cells and better activity against tumor cells will be obtained.