新型抗耐药结核病硫利达嗪衍生物的合成与构效关系评估
Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis.
作者信息
Scalacci Nicolò, Brown Alistair K, Pavan Fernando R, Ribeiro Camila M, Manetti Fabrizio, Bhakta Sanjib, Maitra Arundhati, Smith Darren L, Petricci Elena, Castagnolo Daniele
机构信息
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.
School of Medicine, Pharmacy and Health, Durham University, Wolfson Research Institute, Queens Campus, Stockton on Tees, TS17 6BH, United Kingdom.
出版信息
Eur J Med Chem. 2017 Feb 15;127:147-158. doi: 10.1016/j.ejmech.2016.12.042. Epub 2016 Dec 23.
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.
抗精神病药物硫利达嗪最近被重新定位为一种可能的抗结核药物。硫利达嗪对耐药分枝杆菌显示出抗结核活性，但它具有不良副作用。通过取代哌啶和吩噻嗪部分设计了一个小型硫利达嗪衍生物库，目的是提高抗结核活性并降低细胞毒性作用。在所得化合物中，吲哚衍生物12e显示出比硫利达嗪显著更好的抗分枝杆菌活性，且细胞毒性低15倍。
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