Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer

Detalhes bibliográficos
Autor(a) principal: Jorda, Radek
Data de Publicação: 2019
Outros Autores: Lopes, Susana M. M., Řezníčková, Eva, Ajani, Haresh, Pereira, António V., Gomes, Clara S. B., Pinho e Melo, Teresa M. V. D.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.1016/j.ejmech.2019.05.064
Resumo: S.M.M.L., A.V.P. and T.M.V.D.P.eM. thank Coimbra Chemistry Centre (CQC) , supported by the Portuguese Agency for Scientific Research , “Fundação para a Ciência e a Tecnologia” ( FCT ), through project UID/QUI/00313/2019 . We also acknowledge the UC-NMR facility for obtaining the NMR data ( www.nmrccc.uc.pt ). C.S.B.G. acknowledges the Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES ( UID/QUI/50006/2019 ). The authors (RJ, EŘ) wish to acknowledge the support from the European Regional Development Fund (Project ENOCH, No. CZ.02.1.01/0.0/0.0/16_019/0000868) and Palacký University in Olomouc ( IGA_PrF_2019_013 ).
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spelling Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancerAndrogenGaleteroneProstatepyrazolo[1,5-a]pyridineSteroidPharmacologyDrug DiscoveryOrganic ChemistrySDG 3 - Good Health and Well-beingS.M.M.L., A.V.P. and T.M.V.D.P.eM. thank Coimbra Chemistry Centre (CQC) , supported by the Portuguese Agency for Scientific Research , “Fundação para a Ciência e a Tecnologia” ( FCT ), through project UID/QUI/00313/2019 . We also acknowledge the UC-NMR facility for obtaining the NMR data ( www.nmrccc.uc.pt ). C.S.B.G. acknowledges the Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES ( UID/QUI/50006/2019 ). The authors (RJ, EŘ) wish to acknowledge the support from the European Regional Development Fund (Project ENOCH, No. CZ.02.1.01/0.0/0.0/16_019/0000868) and Palacký University in Olomouc ( IGA_PrF_2019_013 ).The androgen receptor (AR) is a steroid hormone receptor and its high expression and disruption of its regulation are strongly implicated in prostate cancer (PCa) development. One of the current therapies includes application of steroidal antiandrogens leading to blockade of the AR action by the abrogation of AR-mediated signaling. We introduced here novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroidal compounds, described their synthesis based on [8π+2π] cycloaddition reactions of diazafulvenium methides with different steroidal scaffolds and showed their biological evaluation in different prostate cancer cell lines in vitro. Our results showed the ability of novel compounds to suppress the expression of known androgen receptor targets, Nkx3.1 and PSA in two prostate cell lines, 22Rv1 and VCaP. Candidate compound diminished the transcription of AR-regulated genes in the reporter cell line in a concentration-dependent manner. Antiproliferative activity of the most promising steroid was studied by clonogenic assay and induction of apoptosis in treated cells was documented by immunoblot detection of cleaved PARP.LAQV@REQUIMTEDQ - Departamento de QuímicaRUNJorda, RadekLopes, Susana M. M.Řezníčková, EvaAjani, HareshPereira, António V.Gomes, Clara S. B.Pinho e Melo, Teresa M. V. D.2019-07-29T22:41:29Z2019-09-152019-09-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttps://doi.org/10.1016/j.ejmech.2019.05.064eng0223-5234PURE: 14055766http://www.scopus.com/inward/record.url?scp=85066805138&partnerID=8YFLogxKhttps://doi.org/10.1016/j.ejmech.2019.05.064info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:34:58Zoai:run.unl.pt:10362/76917Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:35:42.555128Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
title Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
spellingShingle Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
Jorda, Radek
Androgen
Galeterone
Prostate
pyrazolo[1,5-a]pyridine
Steroid
Pharmacology
Drug Discovery
Organic Chemistry
SDG 3 - Good Health and Well-being
title_short Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
title_full Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
title_fullStr Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
title_full_unstemmed Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
title_sort Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer
author Jorda, Radek
author_facet Jorda, Radek
Lopes, Susana M. M.
Řezníčková, Eva
Ajani, Haresh
Pereira, António V.
Gomes, Clara S. B.
Pinho e Melo, Teresa M. V. D.
author_role author
author2 Lopes, Susana M. M.
Řezníčková, Eva
Ajani, Haresh
Pereira, António V.
Gomes, Clara S. B.
Pinho e Melo, Teresa M. V. D.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv LAQV@REQUIMTE
DQ - Departamento de Química
RUN
dc.contributor.author.fl_str_mv Jorda, Radek
Lopes, Susana M. M.
Řezníčková, Eva
Ajani, Haresh
Pereira, António V.
Gomes, Clara S. B.
Pinho e Melo, Teresa M. V. D.
dc.subject.por.fl_str_mv Androgen
Galeterone
Prostate
pyrazolo[1,5-a]pyridine
Steroid
Pharmacology
Drug Discovery
Organic Chemistry
SDG 3 - Good Health and Well-being
topic Androgen
Galeterone
Prostate
pyrazolo[1,5-a]pyridine
Steroid
Pharmacology
Drug Discovery
Organic Chemistry
SDG 3 - Good Health and Well-being
description S.M.M.L., A.V.P. and T.M.V.D.P.eM. thank Coimbra Chemistry Centre (CQC) , supported by the Portuguese Agency for Scientific Research , “Fundação para a Ciência e a Tecnologia” ( FCT ), through project UID/QUI/00313/2019 . We also acknowledge the UC-NMR facility for obtaining the NMR data ( www.nmrccc.uc.pt ). C.S.B.G. acknowledges the Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES ( UID/QUI/50006/2019 ). The authors (RJ, EŘ) wish to acknowledge the support from the European Regional Development Fund (Project ENOCH, No. CZ.02.1.01/0.0/0.0/16_019/0000868) and Palacký University in Olomouc ( IGA_PrF_2019_013 ).
publishDate 2019
dc.date.none.fl_str_mv 2019-07-29T22:41:29Z
2019-09-15
2019-09-15T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.1016/j.ejmech.2019.05.064
url https://doi.org/10.1016/j.ejmech.2019.05.064
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0223-5234
PURE: 14055766
http://www.scopus.com/inward/record.url?scp=85066805138&partnerID=8YFLogxK
https://doi.org/10.1016/j.ejmech.2019.05.064
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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