Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement

Bo Li; Gaihong Wang; Zhijian Xu; Yong Zhang; Xiangui Huang; Bubing Zeng; Kaixian Chen; Jiye Shi; Heyao Wang; Weiliang Zhu

doi:10.1016/j.ejmech.2014.03.008

Discovery of N-substituted 3-arylisoquinolone derivatives as antitumor agents originating from O-substituted 3-arylisoquinolines via [2,3] or [3,3] rearrangement

Eur J Med Chem. 2014 Apr 22:77:204-10. doi: 10.1016/j.ejmech.2014.03.008. Epub 2014 Mar 6.

Authors

Bo Li¹, Gaihong Wang², Zhijian Xu², Yong Zhang², Xiangui Huang³, Bubing Zeng³, Kaixian Chen², Jiye Shi⁴, Heyao Wang⁵, Weiliang Zhu⁶

Affiliations

¹ Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: [email protected].
² Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
³ School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
⁴ Informatics Department, UCB Pharma, 216 Bath Road, Slough SL1 4EN, United Kingdom. Electronic address: [email protected].
⁵ Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: [email protected].
⁶ Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. Electronic address: [email protected].

PMID: 24637214
DOI: 10.1016/j.ejmech.2014.03.008

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.

Keywords: 3-Arylisoquinolone; Antitumor; [2,3] rearrangement; [3,3] rearrangement.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Discovery*
Drug Screening Assays, Antitumor
HCT116 Cells
Humans
Isoquinolines / chemical synthesis
Isoquinolines / chemistry*
Isoquinolines / pharmacology*
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents
Isoquinolines