Identification of novel piperazinylquinoxaline derivatives as potent phosphoinositide 3-kinase (PI3K) inhibitors.

ABSTRACT:

Background

Development of small-molecule inhibitors targeting phosphoinositide 3-kinase (PI3K) has been an appealing strategy for the treatment of various types of cancers.

Methodology/principal finding

Our approach was to perform structural modification and optimization based on previously identified morpholinoquinoxaline derivative WR1 and piperidinylquinoxaline derivative WR23 with a total of forty-five novel piperazinylquinoxaline derivatives synthesized. Most target compounds showed low micromolar to nanomolar antiproliferative potency against five human cancer cell lines using MTT method. Selected compounds showed potent PI3Kα inhibitory activity in a competitive fluorescent polarization assay, such as compound 22 (IC(50) 40 nM) and 41 (IC(50): 24 nM), which induced ap

SUBMITTER: Wu P 

PROVIDER: S-EPMC3419191 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature