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Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3K? Inhibitors.

ABSTRACT: Three series of novel thienopyrimidine derivatives 9a-l, 15a-l, and 18a-h were designed and synthesized, and their IC50 values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound 9a showed moderate activity with IC50 values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 µM, respectively. The inhibitory activities of compounds 9a and 15a against PI3K? and mTOR kinase were further evaluated. Compound 9a exhibited PI3K? kinase inhibitory activity with IC50 of 9.47 ± 0.63 µM. In addition, docking studies of compounds 9a and 15a were also investigated.

SUBMITTER: Yu L

PROVIDER: S-EPMC6804295 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors.

Yu Lide L Wang Qinqin Q Wang Caolin C Zhang Binliang B Yang Zunhua Z Fang Yuanying Y Zhu Wufu W Zheng Pengwu P

Molecules (Basel, Switzerland) 20190920 19

Three series of novel thienopyrimidine derivatives 9a-l, 15a-l, and 18a-h were designed and synthesized, and their IC50 values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound 9a showed moderate activity with IC50 values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 µM, respect ...[more]

PMID: 31547116

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