摘要
据报道,3,4-二氢萘-1(2H)-酮类化合物具有潜在的抗肿瘤活性和应用价值。以间苯二甲醛、7-甲氧基-3,4-二氢萘-1(2H)-酮、7-氟-3,4-二氢萘-1(2H)-酮为原料,以20%的氢氧化钠溶液为催化剂,通过Claisen-Schmidt缩合反应得到两个苯基桥连的3,4-二氢萘-1(2H)-酮类化合物1和化合物2,并通过NMR、IR、HRMS等波谱手段进行结构表征。MTT法评价了两个化合物对肝癌细胞HepG2、SMMC-7721、QGY-7703和正常肝细胞HHL-5的细胞毒性,ELISA法评价了化合物对LPS诱导的RAW264.7细胞中炎症细胞因子TNF-α、IL-6释放的抑制作用。与阳性对照药相比,化合物1和2显示了较好的抗肝癌活性,特别是氟取代的化合物2对HepG2的IC50值达到2.02μmol/L,对正常细胞HHL-5的毒性较小,且能有效抑制LPS诱导的RAW264.7细胞中炎症细胞因子TNF-α、IL-6的释放,表现出较好的抗炎活性。该研究为开发高效低毒的抗肝癌药物提供了有力素材。
3,4-dihydronaphthalen-1(2 H)-one derivatives have been reported to have potential antitumor activity and application.In this thesis,two phenyl-bridged 3,4-dihydronaphthalen-1(2 H)-one compounds(1)and(2)were synthesized by Claisen-Schmidt condensation reaction of m-phenylenedicarboxaldehyde,7-methoxy-3,4-dihydronaphthalen-1(2 H)-one and 7-fluoro-3,4-dihydronaphthalen-1(2 H)-one.Their structures were characterized by NMR,IR and HRMS.The cytotoxicity and anti-hepatoma activity of both compounds against hepatocellular carcinoma cells HepG2,SMMC-7721,QGY-7703 and normal hepatocytes HHL-5 was evaluated by MTT method.The inhibitory effect of the compounds on LPS-induced release of inflammatory cytokines TNF-αand IL-6 in RAW264.7 cells was evaluated by ELISA.Compared with the positive control drug,both compounds showed better anti-hepatoma activity,especially the fluorine-substituted compound 2 reached an IC 50 value of 2.02μmol/L against HepG2,was less toxic to normal cells HHL-5,and effectively inhibited the release of inflammatory cytokines TNF-αand IL-6 in LPS-induced RAW264.7 cells,showing better anti-inflammatory activity.This study provides a strong material for the development of efficient and low-toxic anti-hepatoma drugs.
作者
刘淑莲
刘连栋
侯云
侯桂革
Liu Shulian;Liu Liandong;Hou Yun;Hou Guige(Shandong Institute of Standardization,Jinan 250000,China;College of Chemistry,Chemical Engineering and Materials Science,Shandong Normal University,Jinan 250014,China;School of Pharmacy,Binzhou Medical University,Yantai 264003,China)
出处
《山东化工》
CAS
2023年第3期1-4,共4页
Shandong Chemical Industry
基金
国家自然科学基金资助项目(81601049)。
关键词
3
4-二氢萘-1(2H)-酮
波谱
抗肝癌
细胞毒性
抗炎
N-methyl-4-piperidinone
spectroscopic methods
anti-hepatoma activity
cytotoxicity
anti-inflammatory
