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Drug discovery and increased potency of antiseptics and disinfectants based on high extracellular pH, the disablement of cellular efflux pumps, and the unexpected synergism therebetween
Drug discovery and increased potency of antiseptics and disinfectants based on high extracellular pH, the disablement of cellular efflux pumps, and the unexpected synergism therebetween
The present invention relates to the enhanced cytoplasmic accumulation of amphipathic weakly basic or amphipathic cationic molecules in prokaryotes and eukaryotes under conditions of high extracellular pH. Furthermore, the present invention relates to the unexpected synergistic effects of high extracellular pH and disrupted cellular efflux mechanisms on the cytoplasmic accumulation of amphipathic weakly basic or amphipathic cationic molecules in prokaryotes and eukaryotes. The present invention relates to methods for increasing the therapeutic potency of amphipathic weakly basic or amphipathic cationic compounds, e.g. antiseptics and disinfectants. Finally, the present invention relates to the exploitation of the aforementioned discoveries in the screening of small molecules, and libraries thereof, for biological activity in prokaryotes and eukaryotes.
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