Cargando…

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

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 super...

Descripción completa

Detalles Bibliográficos
Autores principales: Cao, Shuang, Cao, Ruiyuan, Liu, Xialing, Luo, Xiang, Zhong, Wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274018/
https://www.ncbi.nlm.nih.gov/pubmed/27384552
http://dx.doi.org/10.3390/molecules21070876
_version_ 1783377521403756544
author Cao, Shuang
Cao, Ruiyuan
Liu, Xialing
Luo, Xiang
Zhong, Wu
author_facet Cao, Shuang
Cao, Ruiyuan
Liu, Xialing
Luo, Xiang
Zhong, Wu
author_sort Cao, Shuang
collection PubMed
description 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 IC(50) 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.
format Online
Article
Text
id pubmed-6274018
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62740182018-12-28 Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors Cao, Shuang Cao, Ruiyuan Liu, Xialing Luo, Xiang Zhong, Wu Molecules Article 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 IC(50) 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. MDPI 2016-07-02 /pmc/articles/PMC6274018/ /pubmed/27384552 http://dx.doi.org/10.3390/molecules21070876 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cao, Shuang
Cao, Ruiyuan
Liu, Xialing
Luo, Xiang
Zhong, Wu
Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors
title Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors
title_full Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors
title_fullStr Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors
title_full_unstemmed Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors
title_short Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors
title_sort design, synthesis and biological evaluation of novel benzothiazole derivatives as selective pi3kβ inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274018/
https://www.ncbi.nlm.nih.gov/pubmed/27384552
http://dx.doi.org/10.3390/molecules21070876
work_keys_str_mv AT caoshuang designsynthesisandbiologicalevaluationofnovelbenzothiazolederivativesasselectivepi3kbinhibitors
AT caoruiyuan designsynthesisandbiologicalevaluationofnovelbenzothiazolederivativesasselectivepi3kbinhibitors
AT liuxialing designsynthesisandbiologicalevaluationofnovelbenzothiazolederivativesasselectivepi3kbinhibitors
AT luoxiang designsynthesisandbiologicalevaluationofnovelbenzothiazolederivativesasselectivepi3kbinhibitors
AT zhongwu designsynthesisandbiologicalevaluationofnovelbenzothiazolederivativesasselectivepi3kbinhibitors