title: Design, Synthesis and Evaluation of Naphthalimide Derivatives as Potential Anticancer Agents for Hepatocellular Carcinoma.
abstract: Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound3awith a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound3amoderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound3ainhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that3acould up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound3ais a valuable lead compound worthy of further investigation.
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng 475001, China. gechao1234365@163.com.|Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475001, China. gechao1234365@163.com.
authors.forename: Chaochao
authors.initials: C
authors.lastname: Ge
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475001, China. changlip@126.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Chang
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng 475001, China. 15890173281@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475001, China. kuffychang@163.com.
authors.forename: Congcong
authors.initials: C
authors.lastname: Chang
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng 475001, China. xuxiaojuahn@163.com.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng 475001, China. hhy0926@foxmail.com.
authors.forename: Haoying
authors.initials: H
authors.lastname: He
authors.affiliation: College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475001, China. wangyuxia@henu.edu.cn.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475001, China. fjdwl@hotmail.com.
authors.forename: Fujun
authors.initials: F
authors.lastname: Dai
authors.affiliation: Institute of Chemical Biology, Henan University, Kaifeng 475001, China. xiesq@henu.edu.cn.
authors.forename: Songqiang
authors.initials: S
authors.lastname: Xie
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475001, China. wcjsxq@henu.edu.cn.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D015394:Molecular Structure; D053644:Naphthalimides / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D053644:Naphthalimides
keywords: cell cycle; hepatocellular carcinoma; lung metastasis; naphthalimide; synthesis