Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3K[beta] Inhibitors

A novel series of PI3K[beta] (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, [beta], γ, δ and mTOR (Mammalian target of rapamycin)....

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2016-07, Vol.21 (7), p.876
Main Authors: Cao, Shuang, Cao, Ruiyuan, Liu, Xialing, Luo, Xiang, Zhong, Wu
Format: Article
Language:English
Subjects:
Design
Hydrogen bonds
Kinases
Prostate cancer
Tumors
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Summary:A novel series of PI3K[beta] (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, [beta], 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 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.
ISSN:1420-3049
DOI:10.3390/molecules21070876