Synthesis and biological evaluation of novel 2-arylamino-3-(arylsulfonyl)quinoxalines as PI3Kα inhibitors

Peng Wu; Yi Su; Xiaowen Liu; Lei Zhang; Yong Ye; Jianchao Xu; Shaoyu Weng; Yani Li; Tao Liu; Shufang Huang; Bo Yang; Qiaojun He; Yongzhou Hu

doi:10.1016/j.ejmech.2011.09.015

Synthesis and biological evaluation of novel 2-arylamino-3-(arylsulfonyl)quinoxalines as PI3Kα inhibitors

Eur J Med Chem. 2011 Nov;46(11):5540-8. doi: 10.1016/j.ejmech.2011.09.015. Epub 2011 Sep 17.

Authors

Peng Wu¹, Yi Su, Xiaowen Liu, Lei Zhang, Yong Ye, Jianchao Xu, Shaoyu Weng, Yani Li, Tao Liu, Shufang Huang, Bo Yang, Qiaojun He, Yongzhou Hu

Affiliation

¹ ZJU-ENS Joint laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

PMID: 21945250
DOI: 10.1016/j.ejmech.2011.09.015

Abstract

A series of novel 2-arylamino-3-(arylsulfonyl)quinoxalines was synthesized through a newly developed approach. All synthesized target compounds were screened for their cytotoxicities against cancer cell lines including PC3, A549, HCT116, HL60 and KB. Representative compounds with favorable cytotoxicities were tested for their PI3Kα inhibitory activities. Among the synthesized target compounds, 17 (PI3Kα IC(50): 0.07 μM) displayed the most potent cellular activities (IC(50) values of 0.14 μM, 0.07 μM, 0.95 μM and 0.05 μM against PC3, A549, HCT116 and HL 60, respectively).

MeSH terms

Cell Line, Tumor
Chemistry Techniques, Synthetic*
Class Ia Phosphatidylinositol 3-Kinase / chemistry
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Models, Molecular
Phosphoinositide-3 Kinase Inhibitors*
Protein Conformation
Quinoxalines / chemical synthesis*
Quinoxalines / chemistry
Quinoxalines / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Phosphoinositide-3 Kinase Inhibitors
Quinoxalines
Class Ia Phosphatidylinositol 3-Kinase