Design,Synthesis And Antitumor Activity Of 3-Substituted Indole Derivatives

In the human body,tumors are space-occupying cell tissues formed by abnormal cell proliferation and abnormal apoptosis.According to the spread and metastasis of tumors,tumors can be divided into benign tumors and malignant tumors,among which the cells of malignant tumors can be transferred to any part of the body.Due to the high cost and difficulty of treatment of malignant tumors,the mortality rate of this series of diseases is second only to cardiovascular disease.Therefore,researchers are required to continuously explore and develop new treatment methods to minimize medical expenses and mortality.Among them,drug therapy has always been an ideal treatment for patients.Because certain pharmacophores have certain special effects in the physiological activities of the human body,people designed and synthesized their derivatives based on these pharmacophores and conducted biological activity studies,and found many innovative drugs with effective therapeutic effects.In this paper,we mainly studied the antitumor effects of novel indole derivatives.Indole and its derivatives widely exist in animals and plants,and have a wide range of biological activities.At the substitution site,the substitution at the C-3position of indole is more stable than the substitution at other positions and has more research value.In this paper,we mainly use Fischer indole synthesis method to design and synthesize a series of intermediate and target compounds containing indole structure.Amide or ester is introduced into the C-3 position of indole.Two carbons are separated between the group and indole,and various substituents are introduced into the amide or ester group.Using 5-fluorouracil as a positive reference,ADMET was used to preliminarily predict the drug-like properties and pharmacokinetic properties of the synthesized compound.The CCK-8 experiment was used to detect the cytotoxicity of the synthesized compounds on three kinds of tumor cells(A549,MCF-7,NCI-N87),and discuss their structure-activity relationships.In CCK-8 experiment,compounds 5,9,12,13,14,15,16,19,20 and 23 are selected for cell experiment.At the same concentration,the tested target compound has more inhibitory activity on human gastric cancer cells as a whole.At a concentration of 320 n M,compound 5 has the best inhibitory effect on human gastric cancer cells,compound 19 has the best inhibitory effect on human non-small cell lung cancer cells,and compound 20 has the best inhibitory effect on human breast cancer cells.Except that the inhibitory effect of compound 19 on MCF-7 cells is not clear at the measured concentration,the inhibitory effects of other tested compounds on the tested cancer cells(including the inhibitory effects of compound 19 on NCI-N87 cells and A549 cells)are all higher than 5-fluorouracil.