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...
Autores principales: | , , , , |
---|---|
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 |