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
Descripción
Sumario: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.