Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis.
Scalacci N, Brown AK, Pavan FR, Ribeiro CM, Manetti F, Bhakta S, Maitra A, Smith DL, Petricci E, Castagnolo D.
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.