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We have previously shown that quaternary ammonium salts (QAS) inhibit amino acid transport in Saccharomyces cerevisiae, the degree of inhibition depending on conditions controlling the expression of permease activities [ 1 ]. In view of the structural similarity of some lysosomotropic compounds and QAS, a series of aminoesters of fatty acids were(More)
A set of n-alkyl esters of N,N-dimethylglycine (DMG-n) and their methobromides (DMGM-n) was synthesized, and their activities on yeast Saccharomyces cerevisiae were compared. The compounds differ in the number of carbon atoms in the aliphatic chain. Aminoesters with 12 carbon atoms appeared to be most active. Unlike quaternary ammonium salts previously(More)
The biological activity of lysosomotropic n-alkyl N,N-dimethylglycinates (DMG-n) was compared with that of a quaternary ammonium salt IM (methochloride of DMG-12). The activity of the glycinates appeared to be carbon chain length dependent and was similar at pH 6 and pH 8. Nutritional auxotrophy and respiratory deficiencies have no influence on DMG-n(More)
Multidrug resistance is a major problem in the treatment of infectious diseases caused by bacteria and fungi. One of the basic mechanisms of resistance is active efflux of distinct drugs from cells. Export of toxic compounds from bacterial cells is mediated by proteins of 5 distinct families: MF, SMR, ABC, RND and MATE. The substrate spectrum of efflux(More)
Three quaternary ammonium salts were compared in respect of their ability to select resistant mutants of S. cerevisiae. The mutants tolerating slightly higher IM compound concentration were analysed. They appeared to be the products of nuclear gene mutation segregating monogenically but strongly influenced by genetic background. The mutant IMR when(More)
Pleiotropic drug resistance is a complex phenomenon that involves many proteins that together create a network. One of the common mechanisms of multidrug resistance in eukaryotic cells is the active efflux of a broad range of xenobiotics through ATP-binding cassette (ABC) transporters. Saccharomyces cerevisiae is often used as a model to study such activity(More)
1. Quaternary ammonium salts seem to be potent inhibitors of amino acid uptake inS. cerevisiae. 2. Inhibition is the strongest in yeast with derepressed transport (growth in Yeast Carbon Base medium with proline as the sole nitrogen source). 3. The single-gene resistance to quaternary ammonium salts leads to lowering of transport inhibition. Quaternary(More)
Lysosomotropic agents have antitumor, antifungal and antimicrobial properties. These small, amphiphilic compounds, as weak bases, readily penetrate the lipid bilayer and diffuse into acidic subcellular compartments such as lysosomes or vacuoles. The mechanism of action of lysosomotropic compounds can be distinct, depending on their chemical structure and/or(More)
Quaternary ammonium salts inhibited the growth of yeast especially at pH higher (pH 8) than optimal. It was postulated that compounds integrate with the cell membrane and interfere with its functions. The yeast cell ultrastructure investigated under an electron microscope confirms this hypothesis. A relatively high percentage of cells treated at pH 6 with(More)
Relationships between amino acid auxotrophy and N-dodecyloxy-carboxy-methyl-N-N-N-trimethyl ammonium chloride (IM) sensitivity have been investigated in isogenic yeast strains Saccharomyces cerevisiae and their meiotic segregants. It has been found, that auxotrophy increases the level of sensitivity to this salt markedly. A gene conferring resistance to(More)