Abstract
Identification of drug candidates that enhance pyrazinamide activity from a clinical compound library
Highlights
M. tuberculosis strain H37Ra was cultured in 7H9 medium with 10% albumin-dextrose-catalase (ADC) and 0.05% Tween 80 for 3 months
Several new TB drugs are showing promise in clinical studies, none can replace PZA as they all have to be used together with PZA. 7 Because of the essentiality of PZA and the high cost of developing new drugs, in this study, we explored the idea of identifying drugs that enhance the anti-persister activity of PZA as an economic alternative approach to developing new drugs for improved treatment by screening an clinical drug library against old M. tuberculosis cultures enriched with persisters
In an independent screen with lower 10 μM drug concentration of the clinical drug library combined with 100 μg/ml PZA treated for 3 days, 37 hits were identified to enhance PZA activity, including clinically used drugs clofazimine, rifampin, clotrimazole, doxycycline, tosufloxacin, fleroxacin, nitroxoline, nifuroxime, diacerein, tolfenamic acid, pipemidic acid, benzbromarone, rose bengal, and cod liver oil, etc
Summary
Toremifene a A 3-month-old M. tuberculosis H37Ra culture was treated with different drug candidates (50 μM), PZA (100 μg/ml), or drug candidates plus PZA for 3 days when the viability of the bacteria was determined by transfer to 7H11 plates using a 96-pin replicator for bacterial growth after drug exposure
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