title: 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.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London, SE1 9NH, United Kingdom; Northumbria University Newcastle, Department of Applied Sciences, Ellison Building, Ellison Place, NE1 8ST, Newcastle upon Tyne, United Kingdom.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Scalacci
authors.affiliation: School of Medicine, Pharmacy and Health, Durham University, Wolfson Research Institute, Queens Campus, Stockton on Tees, TS17 6BH, United Kingdom.
authors.forename: Alistair K
authors.initials: AK
authors.lastname: Brown
authors.affiliation: São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, Brazil.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.affiliation: São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Ribeiro
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Via A. Moro 2, 53100, Siena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.affiliation: Mycobacteria Research Laboratory, Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London, WC1E 7HX, United Kingdom.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Bhakta
authors.affiliation: Mycobacteria Research Laboratory, Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London, WC1E 7HX, United Kingdom.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Northumbria University Newcastle, Department of Applied Sciences, Ellison Building, Ellison Place, NE1 8ST, Newcastle upon Tyne, United Kingdom.
authors.forename: Darren L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Via A. Moro 2, 53100, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Petricci
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London, SE1 9NH, United Kingdom. Electronic address: daniele.castagnolo@kcl.ac.uk.
authors.forename: Daniele
authors.initials: D
authors.lastname: Castagnolo
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013881:Thioridazine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D013881:Thioridazine
keywords: Efflux pump; Indole; MDR-TB; Thioridazine; Tuberculosis