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

Abstract

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.

• Authors: Nicolò Scalacci, Alistair K Brown, Fernando R Pavan, Camila M Ribeiro, Fabrizio Manetti, Sanjib Bhakta, Arundhati Maitra, Darren L Smith, Elena Petricci, Daniele Castagnolo
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 127 Pg. 147-158 (Feb 15 2017) ISSN: 1768-3254 [Electronic] France
• PMID: 28039773 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antitubercular Agents
• Thioridazine

Topics

• Antitubercular Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Chemistry Techniques, Synthetic
• Drug Design
• Drug Resistance, Multiple (drug effects)
• Humans
• Mycobacterium tuberculosis (drug effects)
• Structure-Activity Relationship
• Thioridazine (chemical synthesis, chemistry, pharmacology)