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

ABSTRACT: A novel series of PI3K? (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3K?, ?, ?, ? and mTOR (Mammalian target of rapamycin). Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell lines, especially in the prostate cancer cell line. Docking studies indicate the morpholine group in 2-position of benzothiazole is necessary for the potent antitumor activity, which confirms our design is reasonable.

SUBMITTER: Cao S

PROVIDER: S-EPMC6274018 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors.

Cao Shuang S Cao Ruiyuan R Liu Xialing X Luo Xiang X Zhong Wu W

Molecules (Basel, Switzerland) 20160702 7

A novel series of PI3Kβ (Phosphatidylinositol-3-kinases beta subunit) inhibitors with the structure of benzothiazole scaffold have been designed and synthesized. All the compounds have been evaluated for inhibitory activities against PI3Kα, β, γ, δ and mTOR (Mammalian target of rapamycin). Two superior compounds have been further evaluated for the IC50 values against PI3Ks/mTOR. The most promising compound 11 displays excellent anti-proliferative activity and selectivity in multiple cancer cell ...[more]

PMID: 27384552

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