Lysosomotropic N,N- dimethyl alpha-aminoacid n-alkyl esters and their quaternary ammonium salts as plasma membrane and mitochondrial ATPases inhibitors

• Autorzy: Oblak E. , Lachowicz T. M. , Luczynski J. , Witek S.
• Języki publikacji: EN

Abstrakty

EN

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 tested, the activities of the compounds were not pH-dependent; the minimal inhibitory concentrations (MIC) were identical at pH 8 and at pH 6. In contrast to quaternary ammonium salts, aminoesters showed similar effects on respiratory sufficient (rho+) and respiratory deficient (rho°) mutants. When tested on glucose stimulated proton extrusion, aminoesters applied at MIC increased external pH. Aminoesters inhibited the plasma membrane H+-ATPase, whereas they were less inhibitory on the mitochondrial ATPase. In order to further compare the aminoesters and their corresponding quaternary ammonium salts, derivatives of N,N-dimethylalanine (DMAL-n and DMALM-n, respectively) were synthesized. The quaternary ammonium salts appeared to have a higher inhibitory potency than aminoesters, especially at pH 8, and alanine derivatives inhibited growth at a lower concentration than glycine derivatives. Both alanine derivatives of the aminoester and the quaternary ammonium salt inhibited the plasma membrane H+- ATPase at lower concentrations than glycine derivatives, but the alanine aminoester was without a detectable effect on the mitochondrial ATPase.

Słowa kluczowe

EN

lysosomotropic aminoester; n-alkyl ester; N,N-dimethylglycinate; alpha-amino acid; quaternary ammonium salt; plasma membrane; mitochondrial ATPase; Saccharomyces cerevisiae

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2002
• Tom: 07
• Numer: 4
• Opis fizyczny: p.1121-1129,fig.,ref.

Twórcy

autor

Oblak E.

• Institute of Microbiology, University of Wroclaw, Przybyszewskiego 65/73, 51-148 Wroclaw, Poland

autor

Lachowicz T. M.

• Institute of Biotechnology and Environmental Protection, University of Zielona Gora, Monte Cassino 3a, 65-561 Zielona Gora, Poland

autor

Luczynski J.

• Department of Chemistry, Technical University of Wroclaw, 51-148 Wroclaw, Poland

autor

Witek S.

• Department of Chemistry, Technical University of Wroclaw, 51-148 Wroclaw, Poland

Bibliografia

• 1. Lachowicz T. M., Obłąk E. and Piątkowski J. Auxotrophy - stimulated sensitivity to quaternary ammonium salts and its relation to active transport in yeast. Bul. Pol. Acad. Sci. 40 (1992) 173-182.
• 2. Obłąk E., Ułaszewski S., Morawiecki A., Witek S., Witkowska R., Majcher K. and Lachowicz T. M. Quaternary ammonium salt resistant mutants in yeast Saccharomyces cerevisiae. Yeast 5 (Special Issue) (1989) 273-278.
• 3. Obłąk E., Ułaszewski S. and Lachowicz T. M. Mutants of Saccharomyces cerevisiae resistant to a quaternary ammonium salt. Acta Microbiol. Polon. 37 (1988) 261-269.
• 4. Lachowicz T. M., Witkowska R. and Obłąk E. Amino acid auxotrophy increases sensitivity of Saccharomyces cerevisiae to a quaternary ammonium salt IM. Acta Microbiol. Polon. 39 (1990) 157-162.
• 5. Obłąk E., Bącal J. and Lachowicz T. M. A quaternary ammonium salt as an inhibitor of plasma membrane H+-ATPase in yeast Saccharomyces cerevisiae. Cell. Biol. Mol. Lett. 5 (2000) 315 - 324.
• 6. Obłąk E., Lachowicz T. M., Łuczyński J.m and Witek S. Comparative studies of biological activities of the lysosomotropic aminoesters and quaternary ammonium salts on yeast Saccharomyces cerevisiae. Cell. Biol. Mol. Lett. 6 (2001) 871-880.
• 7. Thompson R., Amphiphilic glycine-based esters as soft antimicrobial agents, PhD Thesis, Goeteborg 1992
• 8. Słonimski P. P., Perodin G. and Crought J. H. Ethidium bromide induced mutation of yeast mitochondria: complete transformation of cells into respiratory deficient nonchromosal “petites”. Biochem. Biophys. Res. Commun. 30 (1968) 232.
• 9. Sigler K., Knotkova A. and Kotyk A. Factors governing substrate induced generation and extrusion of protons in the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta. 643 (1981) 572-582.
• 10. Kotyk A. Mechanisms of extracellular acidification by yeast. J. Biophys. 3 (1993) 17-26.
• 11. Dufour J. P. and Goffeau A. Solubilization by lysolecithin and purification of the plasma membrane ATPase of the yeast Schizosaccharomyces pombe. J. Biol. Chem. 253 (1978) 7026-7032.
• 12. Ułaszewski S. Interactions between the gene products of pam1 encoding plasma membrane H+-ATPase, and pdr1 controlling multiple drag resistance in Saccharomyces cerevisiae. Acta Biochim. Polon. 40 (1993) 487-496.
• 13. Lowry O. H., Rosebrough N. J., Farr A. L. and Randall R. J. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193 (1951) 265-275.
• 14. Górska-Poczopko J. and Witek S. Fungicidial properties of some new quaternary ammonium salts. Abh. Akad. Wiss. Deutch. (Berlin) 1 (1982) 271-275.
• 15. Rucka M., Oświęcimska M. and Witek S. New biocides for cooling water treatment. III Quaternary ammonium salts derivatives of glycine esters. Envir. Protect. Eng. 9 No. 3 (1983) 25-31.
• 16. Obłąk E., Lachowicz T. M. and Witek S. DL - leucine transport in a Saccharomyces cerevisiae mutant resistant to quaternary ammonium salts. Folia Microbiol. 41 (1996) 116-119.