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|Title:||MEMBRANE TARGETING XANTHONES - A NEW LEAD AGAINST MYCOBACTERIAL INFECTIONS||Authors:||DEVIKA MUKHERJEE||Keywords:||mycobacteria, resistance, persisters,xanthones||Issue Date:||6-Jan-2017||Citation:||DEVIKA MUKHERJEE (2017-01-06). MEMBRANE TARGETING XANTHONES - A NEW LEAD AGAINST MYCOBACTERIAL INFECTIONS. ScholarBank@NUS Repository.||Abstract:||This thesis first explores the feasibility of membrane targeting xanthones as anti-mycobacterial agents and subsequently, tuning the properties of the amphiphilic cationic xanthone molecules using structure activity relationship studies, is shown. We first test the hypothesis that targeting the cytoplasmic membrane may be an effective way to kill persister mycobacteria and delay the emergence of resistance. A novel xanthone-based antibacterial AM-0016 was assessed against growing and persister mycobacteria. Exposure to AM-0016 resulted in rapid collapse of the membrane potential and imaging revealed deformation of the cell envelope, indicating this molecule targets the membrane. Next, using Structure activity relationship studies for the rational design of xanthones we were able to show improved activity of compounds, upon rational design of membrane targeting xanthone molecules. In doing so, we have shown that optimization of xanthone compounds could facilitate the development of safe and effective novel peptide therapeutics for application in mycobacterial infections.||URI:||http://scholarbank.nus.edu.sg/handle/10635/135881|
|Appears in Collections:||Ph.D Theses (Open)|
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