title: Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anti-cancer agents for lung cancer.
abstract: The nuclear factor-kappa B (NF-κB) signaling pathway has been targeted for the therapy of various cancers, including lung cancer. EF24 was considered as a potent inhibitor of NF-κB signaling pathway. In this study, a series of asymmetric EF24 analogues were synthesized and evaluated for their anti-cancer activity against three lung cancer cell lines (A549, LLC, H1650). Most of the compounds exhibited good anti-tumor activity. Among them, compound 81 showed greater cytotoxicity than EF24. Compound 81 also possessed a potent anti-migration and anti-proliferative ability against A549 cells in a concentration-dependent manner. Moreover, compound 81 induced lung cancer cells death by inhibiting NF-κB signaling pathway, and activated the JNK-mitochondrial apoptotic pathway by increasing reactive oxygen species (ROS) generation resulting in apoptosis. In summary, compound 81 is a valuable candidate for anti-lung cancer therapy.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Shoubiao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Shi
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Ren
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Di
authors.initials: D
authors.lastname: Yun
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Jiabing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China; College of Information Science and Computer Engineering, The First Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: lwlwzmu@163.com.
authors.forename: Wulan
authors.initials: W
authors.lastname: Li
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China; Institute of Tissue Transplantation and Immunology, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Key Laboratory of Molecule Immunology and Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, 510632, China. Electronic address: wxpjnu@163.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China. Electronic address: wjzwzmc@126.com.
authors.forename: Peihong
authors.initials: P
authors.lastname: Qiu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical Universtiy, Wenzhou, Zhejiang 325035, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D016328:NF-kappa B; D010881:Piperidones; D017382:Reactive Oxygen Species
keywords: Anti-cancer activity; Asymmetric EF24 analogues; NF-κB; ROS; Synthesis