| Literature DB >> 28654257 |
Gabriela Seydlová1, Radek Pohl2, Eva Zborníková2,3, Marcel Ehn2, Ondřej Šimák2, Natalya Panova4, Milan Kolář5, Kateřina Bogdanová5, Renata Večeřová5, Radovan Fišer1, Hana Šanderová4, Dragana Vítovská4, Petra Sudzinová1,4, Jiří Pospíšil1,4, Oldřich Benada4, Tomáš Křížek3, David Sedlák6, Petr Bartůněk6, Libor Krásný4, Dominik Rejman2.
Abstract
The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report the synthesis of novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO II display excellent activities against Gram-positive and -negative bacteria, including pathogens and multiresistant strains. We describe their mechanism of action-plasmatic membrane pore-forming activity selective for bacteria. Importantly, LPPO II neither damage nor cross the eukaryotic plasmatic membrane at their bactericidal concentrations. Further, we demonstrate LPPO II have low propensity for resistance development, likely due to their rapid membrane-targeting mode of action. Finally, we reveal that LPPO II are not toxic to either eukaryotic cells or model animals when administered orally or topically. Collectively, these results suggest that LPPO II are highly promising compounds for development into pharmaceuticals.Entities:
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Year: 2017 PMID： 28654257 DOI： 10.1021/acs.jmedchem.7b00355
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446