Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors

Detalhes bibliográficos
Autor(a) principal: Jin, Qing-Hao
Data de Publicação: 2020
Outros Autores: Chen, Wen-Bo, Xia, Ya-Nan, Liu, Bing-Yu, Guan, Li-Ping
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Pharmaceutical Sciences
Texto Completo: https://www.revistas.usp.br/bjps/article/view/181157
Resumo: A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2–23.2 µg/mL) and PTP1B (IC50 = 2.9–21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.
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spelling Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors: Dioxoindolin-N-phenylacetamideCDC25BPTP1BPhosphatase inhibitorsEnzyme kineticsA series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2–23.2 µg/mL) and PTP1B (IC50 = 2.9–21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2020-12-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/18115710.1590/s2175-97902019000400222Brazilian Journal of Pharmaceutical Sciences; Vol. 56 (2020); e00222Brazilian Journal of Pharmaceutical Sciences; v. 56 (2020); e00222Brazilian Journal of Pharmaceutical Sciences; Vol. 56 (2020); e002222175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/181157/168103Copyright (c) 2020 Brazilian Journal of Pharmaceutical Scienceshttp://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessJin, Qing-Hao Chen, Wen-Bo Xia, Ya-Nan Liu, Bing-Yu Guan, Li-Ping 2021-06-12T19:46:54Zoai:revistas.usp.br:article/181157Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2021-06-12T19:46:54Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
title Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
spellingShingle Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
Jin, Qing-Hao
: Dioxoindolin-N-phenylacetamide
CDC25B
PTP1B
Phosphatase inhibitors
Enzyme kinetics
title_short Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
title_full Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
title_fullStr Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
title_full_unstemmed Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
title_sort Biological evaluation of 2,3-dioxoindolin-N-phenylacetamide derivatives as potent CDC25B and PTP1B phosphatase inhibitors
author Jin, Qing-Hao
author_facet Jin, Qing-Hao
Chen, Wen-Bo
Xia, Ya-Nan
Liu, Bing-Yu
Guan, Li-Ping
author_role author
author2 Chen, Wen-Bo
Xia, Ya-Nan
Liu, Bing-Yu
Guan, Li-Ping
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Jin, Qing-Hao
Chen, Wen-Bo
Xia, Ya-Nan
Liu, Bing-Yu
Guan, Li-Ping
dc.subject.por.fl_str_mv : Dioxoindolin-N-phenylacetamide
CDC25B
PTP1B
Phosphatase inhibitors
Enzyme kinetics
topic : Dioxoindolin-N-phenylacetamide
CDC25B
PTP1B
Phosphatase inhibitors
Enzyme kinetics
description A series of 2,3-dioxoindolin-N-phenylacetamide derivatives was evaluated for inhibitory activity against CDC25B and PTP1B enzymes. Most of the derivatives showed inhibitory activity against CDC25B (IC50 = 3.2–23.2 µg/mL) and PTP1B (IC50 = 2.9–21.4 µg/mL). Compound 2h showed the most inhibitory activity in vitro with IC50 values of 3.2 and 2.9 µg/mL against CDC25B and PTP1B, respectively, compared with the reference drugs Na3VO4 (IC50 = 2.7 µg/mL) and oleanolic acid (IC50 = 2.3 µg/mL). The results of selectivity experiments showed that the 2,3-dioxoindolin-N-phenylacetamide derivatives were selective inhibitors against CDC25B and PTP1B. Enzyme kinetic experiments demonstrated that compound 2h was a specific inhibitor with the typical characteristics of a mixed inhibitor. In cytotoxic activity assays compound 2h had potent activity against A549, HeLa, and HCT116 cell lines. In addition, compound 2h showed potent tumor inhibitory activity in a colo205 xenograft model in vivo.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-09
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/bjps/article/view/181157
10.1590/s2175-97902019000400222
url https://www.revistas.usp.br/bjps/article/view/181157
identifier_str_mv 10.1590/s2175-97902019000400222
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/bjps/article/view/181157/168103
dc.rights.driver.fl_str_mv Copyright (c) 2020 Brazilian Journal of Pharmaceutical Sciences
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2020 Brazilian Journal of Pharmaceutical Sciences
http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
dc.source.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences; Vol. 56 (2020); e00222
Brazilian Journal of Pharmaceutical Sciences; v. 56 (2020); e00222
Brazilian Journal of Pharmaceutical Sciences; Vol. 56 (2020); e00222
2175-9790
1984-8250
reponame:Brazilian Journal of Pharmaceutical Sciences
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Brazilian Journal of Pharmaceutical Sciences
collection Brazilian Journal of Pharmaceutical Sciences
repository.name.fl_str_mv Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)
repository.mail.fl_str_mv bjps@usp.br||elizabeth.igne@gmail.com
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