title: Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement.
abstract: The present study discovers multiple N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement. The current [2,3] rearrangement of epoxy or acetal O-substituents converting to diol or alcohol N-substituents can be promoted by silica gel or by diluted hydrochloric acid, which is distinct from previously reported [2,3] rearrangements. Some of the derivatives displayed comparable or even stronger cytotoxicity than sorafenib and vemurafenib on HCT116 colon carcinoma and A375 melanoma cell lines. Therefore, the rearrangement via intramolecular carbon-oxygen bond cleavage and carbon-nitrogen bond formation should be a useful approach for developing novel anticancer drugs derived from isoquinolones.
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: boli@simm.ac.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Gaihong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Xiangui
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Bubing
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
authors.affiliation: Informatics Department, UCB Pharma, 216 Bath Road, Slough SL1 4EN, United Kingdom. Electronic address: Jiye.Shi@ucb.com.
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: hywang@mail.shcnc.ac.cn.
authors.forename: Heyao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: wlzhu@mail.shcnc.ac.cn.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines
keywords: 3-Arylisoquinolone; Antitumor; [2,3] rearrangement; [3,3] rearrangement