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Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition.

Authors :
Li M
Wang D
Li Q
Luo F
Zhong T
Wu H
Xiong L
Yuan M
Su M
Fan Y
Source :
International journal of molecular sciences [Int J Mol Sci] 2023 Apr 06; Vol. 24 (7). Date of Electronic Publication: 2023 Apr 06.
Publication Year :
2023

Abstract

Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by <superscript>1</superscript> H NMR, <superscript>13</superscript> C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which 13k is the most potent compound with IC <subscript>50</subscript> values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, 13k induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC <subscript>50</subscript> value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor.

Details

Language :
English
ISSN :
1422-0067
Volume :
24
Issue :
7
Database :
MEDLINE
Journal :
International journal of molecular sciences
Publication Type :
Academic Journal
Accession number :
37047827
Full Text :
https://doi.org/10.3390/ijms24076851