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

Nicolò Scalacci; Alistair Brown; Fernando Pavan; Camila Ribeiro; Fabrizio Manetti; Sanjib Bhakta; Arundhati Maitra; Darren Smith; Elena Petricci; Daniele Castagnolo

doi:10.1016/j.ejmech.2016.12.042

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

Nicolò Scalacci, Alistair Brown, Fernando Pavan, Camila Ribeiro, Fabrizio Manetti, Sanjib Bhakta, Arundhati Maitra, Darren Smith, Elena Petricci, Daniele Castagnolo^*

^*Corresponding author for this work

Applied Sciences Department

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

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.

Original language	English
Pages (from-to)	147-158
Journal	European Journal of Medicinal Chemistry
Volume	127
Early online date	23 Dec 2016
DOIs	https://doi.org/10.1016/j.ejmech.2016.12.042
Publication status	Published - 15 Feb 2017

Keywords

Thioridazine
Tuberculosis
MDR-TB
Efflux pump
Indole

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2016.12.042

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Cite this

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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.",

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author = "Nicol{\`o} Scalacci and Alistair Brown and Fernando Pavan and Camila Ribeiro and Fabrizio Manetti and Sanjib Bhakta and Arundhati Maitra and Darren Smith and Elena Petricci and Daniele Castagnolo",

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doi = "10.1016/j.ejmech.2016.12.042",

language = "English",

volume = "127",

pages = "147--158",

journal = "European Journal of Medicinal Chemistry",

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TY - JOUR

T1 - Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis

AU - Scalacci, Nicolò

AU - Brown, Alistair

AU - Pavan, Fernando

AU - Ribeiro, Camila

AU - Manetti, Fabrizio

AU - Bhakta, Sanjib

AU - Maitra, Arundhati

AU - Smith, Darren

AU - Petricci, Elena

AU - Castagnolo, Daniele

PY - 2017/2/15

Y1 - 2017/2/15

N2 - 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.

AB - 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.

KW - Thioridazine

KW - Tuberculosis

KW - MDR-TB

KW - Efflux pump

KW - Indole

U2 - 10.1016/j.ejmech.2016.12.042

DO - 10.1016/j.ejmech.2016.12.042

M3 - Article

SN - 0223-5234

VL - 127

SP - 147

EP - 158

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

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

Abstract

Keywords

UN SDGs

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