A combination screening to identify enhancers of para-aminosalicylic acid against Mycobacterium tuberculosisopen access
- Heo, Jinyeong; Koh, Dahae; Woo, Minjeong; Kwon, Doyoon; de Almeida Falcao, Virginia Carla; Wood, Connor; Lee, Honggun; Kim, Kideok; Choi, Inhee; Jang, Jichan; Brodin, Priscille; Shum, David; Delorme, Vincent
- Issue Date
- NATURE PORTFOLIO
- SCIENTIFIC REPORTS, v.12, no.1
- Journal Title
- SCIENTIFIC REPORTS
- Para-aminosalicylic acid (PAS) is an antibiotic that was largely used for the multi-therapy of tuberculosis in the twentieth century. To try to overcome the inconvenience of its low efficacy and poor tolerance, we searched for novel chemical entities able to synergize with PAS using a combination screening against growing axenic Mycobacterium tuberculosis. The screening was performed at a sub-inhibitory concentration of PAS on a library of about 100,000 small molecules. Selected hit compounds were analyzed by dose-response and further probed with an intracellular macrophage assay. Scaffolds with potential additive effect with PAS are reported, opening interesting prospects for mechanism of action studies. We also report here evidence of a yet unknown bio-activation mechanism, involving activation of pyrido[1,2-a]pyrimidin-4-one (PP) derivatives through the Rv3087 protein.
- Files in This Item
- There are no files associated with this item.
- Appears in
- 자연과학대학 > Division of Life Sciences > Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.