Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UNESP |
| Texto Completo: | http://dx.doi.org/10.1016/j.ejmech.2016.12.042 http://hdl.handle.net/11449/178534 |
Resumo: | 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. |
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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 LondonScalacci, Nicol�Brown, Alistair K.Pavan, Fernando R. [UNESP]Ribeiro, Camila M. [UNESP]Manetti, FabrizioBhakta, SanjibMaitra, ArundhatiSmith, Darren L.Petricci, ElenaCastagnolo, Daniele2018-12-11T17:30:49Z2018-12-11T17:30:49Z2017-01-01info: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/openAccess2023-12-12T06:23:19Zoai:repositorio.unesp.br:11449/178534Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-12T06:23:19Repositório 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 |
| 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.contributor.author.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 |
| 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 |
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Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
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Universidade Estadual Paulista (UNESP) |
| instacron_str |
UNESP |
| institution |
UNESP |
| reponame_str |
Repositório Institucional da UNESP |
| collection |
Repositório Institucional da UNESP |
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Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
| repository.mail.fl_str_mv |
|
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1797789983167217664 |