Issue 51, 2019, Issue in Progress

Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors

Abstract

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 IC50 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.

Graphical abstract: Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors

Supplementary files

Article information

Article type
Paper
Submitted
09 Aug 2019
Accepted
09 Sep 2019
First published
18 Sep 2019
This article is Open Access
Creative Commons BY license

RSC Adv., 2019,9, 29579-29589

Synthesis and bioevaluation of thienopyrimidines bearing a pyrazoline unit as selective PI3Kα inhibitors

L. Lai, Q. Wang, B. Zhang, Z. Xiao, Z. Yang, Q. Yang, Z. Luo, W. Zhu and S. Xu, RSC Adv., 2019, 9, 29579 DOI: 10.1039/C9RA06192D

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