Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition
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-...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6851 |
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| author | Mei Li Daoping Wang Qing Li Fang Luo Ting Zhong Hongshan Wu Liang Xiong Meitao Yuan Mingzhi Su Yanhua Fan |
| author_facet | Mei Li Daoping Wang Qing Li Fang Luo Ting Zhong Hongshan Wu Liang Xiong Meitao Yuan Mingzhi Su Yanhua Fan |
| author_sort | Mei Li |
| collection | DOAJ |
| description | 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 <sup>1</sup>H NMR, <sup>13</sup>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 <b>13k</b> is the most potent compound with IC<sub>50</sub> values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, <b>13k</b> induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC<sub>50</sub> value of 1.94 nM. These results suggested that compound <b>13k</b> might serve as a lead compound for the development of PI3Kα inhibitor. |
| first_indexed | 2024-03-11T05:33:41Z |
| format | Article |
| id | doaj.art-458aae3d32d044efa88bfe15bf080133 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:33:41Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-458aae3d32d044efa88bfe15bf0801332023-11-17T16:56:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01247685110.3390/ijms24076851Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα InhibitionMei Li0Daoping Wang1Qing Li2Fang Luo3Ting Zhong4Hongshan Wu5Liang Xiong6Meitao Yuan7Mingzhi Su8Yanhua Fan9State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaAberrant 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 <sup>1</sup>H NMR, <sup>13</sup>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 <b>13k</b> is the most potent compound with IC<sub>50</sub> values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, <b>13k</b> induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC<sub>50</sub> value of 1.94 nM. These results suggested that compound <b>13k</b> might serve as a lead compound for the development of PI3Kα inhibitor.https://www.mdpi.com/1422-0067/24/7/6851cell cycle arrestcell apoptosisPI3Kα inhibitorquinazolineimidazo[1,2-a]pyridine |
| spellingShingle | Mei Li Daoping Wang Qing Li Fang Luo Ting Zhong Hongshan Wu Liang Xiong Meitao Yuan Mingzhi Su Yanhua Fan Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition International Journal of Molecular Sciences cell cycle arrest cell apoptosis PI3Kα inhibitor quinazoline imidazo[1,2-a]pyridine |
| title | Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition |
| title_full | Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition |
| title_fullStr | Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition |
| title_full_unstemmed | Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition |
| title_short | Design, Synthesis and Biological Evaluation of 6-(Imidazo[1,2-a]pyridin-6-yl)quinazoline Derivatives as Anticancer Agents via PI3Kα Inhibition |
| title_sort | design synthesis and biological evaluation of 6 imidazo 1 2 a pyridin 6 yl quinazoline derivatives as anticancer agents via pi3kα inhibition |
| topic | cell cycle arrest cell apoptosis PI3Kα inhibitor quinazoline imidazo[1,2-a]pyridine |
| url | https://www.mdpi.com/1422-0067/24/7/6851 |
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