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

2019-09-15Artigo científico Acesso aberto
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dc.contributor.authorJorda, Radek
dc.contributor.authorLopes, Susana M. M.
dc.contributor.authorŘezníčková, Eva
dc.contributor.authorAjani, Haresh
dc.contributor.authorPereira, António V.
dc.contributor.authorGomes, Clara S. B.
dc.contributor.authorPinho e Melo, Teresa M. V. D.
dc.contributor.institutionLAQV@REQUIMTE
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.pblElsevier Masson
dc.date.accessioned2019-07-29T22:41:29Z
dc.date.available2019-07-29T22:41:29Z
dc.date.issued2019-09-15
dc.descriptionS.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 ).
dc.description.abstractThe 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.en
dc.description.versionauthorsversion
dc.description.versionpublished
dc.format.extent9
dc.format.extent1881259
dc.identifier.doi10.1016/j.ejmech.2019.05.064
dc.identifier.issn0223-5234
dc.identifier.otherPURE: 14055766
dc.identifier.otherPURE UUID: 850b8077-ffea-4d93-acc1-ef56104b43b2
dc.identifier.otherScopus: 85066805138
dc.identifier.otherPubMed: 31181481
dc.identifier.otherORCID: /0000-0003-3672-0045/work/64041169
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=85066805138&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/85066805138
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAndrogen
dc.subjectGaleterone
dc.subjectProstate
dc.subjectpyrazolo[1,5-a]pyridine
dc.subjectSteroid
dc.subjectPharmacology
dc.subjectDrug Discovery
dc.subjectOrganic Chemistry
dc.subjectSDG 3 - Good Health and Well-being
dc.titleTetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate canceren
dc.typejournal article
degois.publication.firstPage168
degois.publication.lastPage176
degois.publication.titleEuropean Journal of Medicinal Chemistry
degois.publication.volume178
dspace.entity.typePublication
rcaap.rightsopenAccess

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