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Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors
A series of thienopyrimidines containing a pyrazoline unit (4a–d, 7a–d and 13a–l) were designed and synthesized. The target compounds were evaluated for antiproliferative activity against A549, HepG2 and MCF-7 cancer cell lines. Among the twenty target compounds, most of them exhibited excellent ant...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072010/ https://www.ncbi.nlm.nih.gov/pubmed/35531514 http://dx.doi.org/10.1039/c9ra06192d |
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author | Lai, Luogen Wang, Qinqin Zhang, Binliang Xiao, Zhen Yang, Zunhua Yang, Qi Luo, Zixin Zhu, Wufu Xu, Shan |
author_facet | Lai, Luogen Wang, Qinqin Zhang, Binliang Xiao, Zhen Yang, Zunhua Yang, Qi Luo, Zixin Zhu, Wufu Xu, Shan |
author_sort | Lai, Luogen |
collection | PubMed |
description | A series of thienopyrimidines containing a pyrazoline unit (4a–d, 7a–d and 13a–l) were designed and synthesized. The target compounds were evaluated for antiproliferative activity against A549, HepG2 and MCF-7 cancer cell lines. Among the twenty target compounds, most of them exhibited excellent antiproliferative activity against one or several cancer cell lines. Compound 13f showed the best activity against A549, MCF-7 and HepG2 cancer cell lines, with IC(50) values of 2.84 ± 0.09 μM, 2.88 ± 0.43 μM and 2.08 ± 0.36 μM, respectively. Four selected compounds (13c, 13f, 13g and 13h) were further evaluated for their inhibitory activity against the PI3Kα/mTOR protein kinase. Moreover, time-dependent and dose-dependent experiments, AO fluorescence staining, Annexin V-FITC/PI staining and docking studies were carried out in this study. The results indicated that compound 13f may be a potential selective PI3Kα inhibitor. |
format | Online Article Text |
id | pubmed-9072010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90720102022-05-06 Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors Lai, Luogen Wang, Qinqin Zhang, Binliang Xiao, Zhen Yang, Zunhua Yang, Qi Luo, Zixin Zhu, Wufu Xu, Shan RSC Adv Chemistry A series of thienopyrimidines containing a pyrazoline unit (4a–d, 7a–d and 13a–l) were designed and synthesized. The target compounds were evaluated for antiproliferative activity against A549, HepG2 and MCF-7 cancer cell lines. Among the twenty target compounds, most of them exhibited excellent antiproliferative activity against one or several cancer cell lines. Compound 13f showed the best activity against A549, MCF-7 and HepG2 cancer cell lines, with IC(50) values of 2.84 ± 0.09 μM, 2.88 ± 0.43 μM and 2.08 ± 0.36 μM, respectively. Four selected compounds (13c, 13f, 13g and 13h) were further evaluated for their inhibitory activity against the PI3Kα/mTOR protein kinase. Moreover, time-dependent and dose-dependent experiments, AO fluorescence staining, Annexin V-FITC/PI staining and docking studies were carried out in this study. The results indicated that compound 13f may be a potential selective PI3Kα inhibitor. The Royal Society of Chemistry 2019-09-18 /pmc/articles/PMC9072010/ /pubmed/35531514 http://dx.doi.org/10.1039/c9ra06192d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Lai, Luogen Wang, Qinqin Zhang, Binliang Xiao, Zhen Yang, Zunhua Yang, Qi Luo, Zixin Zhu, Wufu Xu, Shan Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors |
title | Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors |
title_full | Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors |
title_fullStr | Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors |
title_full_unstemmed | Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors |
title_short | Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors |
title_sort | synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective pi3kα inhibitors |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072010/ https://www.ncbi.nlm.nih.gov/pubmed/35531514 http://dx.doi.org/10.1039/c9ra06192d |
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