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

Scalacci, Nicolï¿½; Brown, Alistair K.; Pavan, Fernando R. [UNESP]; Ribeiro, Camila M. [UNESP]; Manetti, Fabrizio; Bhakta, Sanjib; Maitra, Arundhati; Smith, Darren L.; Petricci, Elena; Castagnolo, Daniele

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

Arquivos

2-s2.0-85007140997.pdf (1009.78 KB)

Data

2017-01-01

Autores

Tipo

Artigo

Direito de acesso

Acesso aberto

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.