Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis

The neuroleptic drug thioridazine has been recently repositioned as possible anti-tubercular drug. Thioridazine showed anti-tubercular activity against drug resistant mycobacteria but it is endowed with adverse side effects. A small library of thioridazine derivatives has been designed through the r...

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Detalles Bibliográficos
Autores: Scalacci, Nicol�, Brown, Alistair K., Pavan, Fernando R. [UNESP], Ribeiro, Camila M. [UNESP], Manetti, Fabrizio, Bhakta, Sanjib, Maitra, Arundhati, Smith, Darren L., Petricci, Elena, Castagnolo, Daniele
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:Brasil
Institución:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/178534
Acceso en línea:http://dx.doi.org/10.1016/j.ejmech.2016.12.042
http://hdl.handle.net/11449/178534
Access Level:acceso abierto
Palabra clave:Efflux pump
Indole
MDR-TB
Thioridazine
Tuberculosis
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spelling Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosisEfflux pumpIndoleMDR-TBThioridazineTuberculosisThe neuroleptic drug thioridazine has been recently repositioned as possible anti-tubercular drug. Thioridazine showed anti-tubercular activity against drug resistant mycobacteria but it is endowed with adverse side effects. A small library of thioridazine derivatives has been designed through the replacement of the piperidine and phenothiazine moieties, with the aim to improve the anti-tubercular activity and to reduce the cytotoxic effects. Among the resulting compounds, the indole derivative 12e showed an antimycobacterial activity significantly better than thioridazine and a cytotoxicity 15-fold lower.Royal Society of ChemistryInstitute of Pharmaceutical Science King's College London, 150 Stamford StreetNorthumbria University Newcastle Department of Applied Sciences, Ellison Building, Ellison PlaceSchool of Medicine Pharmacy and Health Durham University Wolfson Research Institute Queens Campus, Stockton on TeesS�o Paulo State University (UNESP) School of Pharmaceutical SciencesDipartimento di Biotecnologie, Chimica e Farmacia, Via A. Moro 2Mycobacteria Research Laboratory Department of Biological Sciences Institute of Structural and Molecular Biology University of London, Birkbeck, Malet StreetS�o Paulo State University (UNESP) School of Pharmaceutical SciencesKing's College LondonNorthumbria University NewcastleQueens CampusUniversidade Estadual Paulista (Unesp)Dipartimento di BiotecnologieUniversity of London2018-12-11T17:30:49Z2018-12-11T17:30:49Z2017-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article147-158application/pdfhttp://dx.doi.org/10.1016/j.ejmech.2016.12.042European Journal of Medicinal Chemistry, v. 127, p. 147-158.1768-32540223-5234http://hdl.handle.net/11449/17853410.1016/j.ejmech.2016.12.0422-s2.0-850071409972-s2.0-85007140997.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengEuropean Journal of Medicinal Chemistry1,266info:eu-repo/semantics/openAccessScalacci, Nicol�Brown, Alistair K.Pavan, Fernando R. [UNESP]Ribeiro, Camila M. [UNESP]Manetti, FabrizioBhakta, SanjibMaitra, ArundhatiSmith, Darren L.Petricci, ElenaCastagnolo, Daniele2025-03-29T05:02:40Zoai:repositorio.unesp.br:11449/178534Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-03-29T05:02:40Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
title Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
spellingShingle Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
Scalacci, Nicol�
Efflux pump
Indole
MDR-TB
Thioridazine
Tuberculosis
title_short Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
title_full Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
title_fullStr Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
title_full_unstemmed Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
title_sort Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
dc.creator.none.fl_str_mv Scalacci, Nicol�
Brown, Alistair K.
Pavan, Fernando R. [UNESP]
Ribeiro, Camila M. [UNESP]
Manetti, Fabrizio
Bhakta, Sanjib
Maitra, Arundhati
Smith, Darren L.
Petricci, Elena
Castagnolo, Daniele
author Scalacci, Nicol�
author_facet Scalacci, Nicol�
Brown, Alistair K.
Pavan, Fernando R. [UNESP]
Ribeiro, Camila M. [UNESP]
Manetti, Fabrizio
Bhakta, Sanjib
Maitra, Arundhati
Smith, Darren L.
Petricci, Elena
Castagnolo, Daniele
author_role author
author2 Brown, Alistair K.
Pavan, Fernando R. [UNESP]
Ribeiro, Camila M. [UNESP]
Manetti, Fabrizio
Bhakta, Sanjib
Maitra, Arundhati
Smith, Darren L.
Petricci, Elena
Castagnolo, Daniele
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv King's College London
Northumbria University Newcastle
Queens Campus
Universidade Estadual Paulista (Unesp)
Dipartimento di Biotecnologie
University of London
dc.subject.por.fl_str_mv Efflux pump
Indole
MDR-TB
Thioridazine
Tuberculosis
topic Efflux pump
Indole
MDR-TB
Thioridazine
Tuberculosis
description The neuroleptic drug thioridazine has been recently repositioned as possible anti-tubercular drug. Thioridazine showed anti-tubercular activity against drug resistant mycobacteria but it is endowed with adverse side effects. A small library of thioridazine derivatives has been designed through the replacement of the piperidine and phenothiazine moieties, with the aim to improve the anti-tubercular activity and to reduce the cytotoxic effects. Among the resulting compounds, the indole derivative 12e showed an antimycobacterial activity significantly better than thioridazine and a cytotoxicity 15-fold lower.
publishDate 2017
dc.date.none.fl_str_mv 2017-01-01
2018-12-11T17:30:49Z
2018-12-11T17:30:49Z
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 http://dx.doi.org/10.1016/j.ejmech.2016.12.042
European Journal of Medicinal Chemistry, v. 127, p. 147-158.
1768-3254
0223-5234
http://hdl.handle.net/11449/178534
10.1016/j.ejmech.2016.12.042
2-s2.0-85007140997
2-s2.0-85007140997.pdf
url http://dx.doi.org/10.1016/j.ejmech.2016.12.042
http://hdl.handle.net/11449/178534
identifier_str_mv European Journal of Medicinal Chemistry, v. 127, p. 147-158.
1768-3254
0223-5234
10.1016/j.ejmech.2016.12.042
2-s2.0-85007140997
2-s2.0-85007140997.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv European Journal of Medicinal Chemistry
1,266
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 147-158
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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score 15,301603

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