Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition
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Published:2023-04-06
Issue:7
Volume:24
Page:6851
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Li Mei12,
Wang Daoping12,
Li Qing12,
Luo Fang12,
Zhong Ting12,
Wu Hongshan12,
Xiong Liang12,
Yuan Meitao12,
Su Mingzhi12,
Fan Yanhua12
Affiliation:
1. State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China
2. The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China
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 1H NMR, 13C 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 IC50 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 IC50 value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor.
Funder
National Natural Science Foundation of China
Merit-based Funding Program for Innovation and Entrepreneurship of High-level Overseas Talents of Guizhou Province
Natural Science Foundation of Guizhou Provincial Science and Technology Projects
Science and Technology Plan Project of Guizhou Province, China
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
2 articles.
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