Facilitated diffusion of glucosamine-6-phosphate synthase inhibitors enhances their antifungal activity

• Autorzy: Janiak A. , Cybulska B. , Szlinder-Richert J. , Borowski E. , Milewski S.
• Języki publikacji: EN

Abstrakty

EN

N3-(4-Methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP) and 2-amino-2- deoxy-D-glucitol-6-phosphate (ADGP) are strong inhibitors of the essential fungal en­zyme, glucosamine-6-phosphate synthase, but their antifungal activity is poor, due to slow penetration of these agents through the cytoplasmic membrane. In the present studies we have exploited the possibility of enhancement of ADGP and FMDP antifungal activity by improving their transport properties. It has been found that membrane-permeabilising polyene macrolides amphotericin B (AMB) and its .N-methyl-^-fructosyl methyl ester derivative (MF-AME), at subinhibitory concentra­tions, facilitate diffusion of ADGP through the fungal cell membrane, thus allowing a decrease of its minimal inhibitory concentration (MIC). Synergistic effects have been observed for combinations of ADGP with AMB or MF-AME. Fractional inhibitory con­centration (FIC) indexes, determined against a number of Candida spp., have been in the 0.18-0.81 range. Weak antifungal synergistic effects have been found for combi­nations of FMDP with AMB or MF-AME.ADGP can be easily encapsulated into unilamellar lipid vesicles. Liposomal preparations of ADGP demonstrated stronger antifungal activity against some fungal strains than free ADGP.

Słowa kluczowe

EN

liposome; antifungal activity; cytoplasmic membrane; diffusion; 2-amino-2-deoxy-D-glucitol-6-phosphate; fungal enzyme; glucosamine-6-phosphate synthase; synergism; N3-[-4-methoxyfumaroyl]-L-2,3-diaminopropanoic acid

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2002
• Tom: 49
• Numer: 1
• Opis fizyczny: p.77-86,fig.

Twórcy

autor

Janiak A.

• Technical University of Gdansk, Gdansk, Poland

autor

Cybulska B.

autor

Szlinder-Richert J.

autor

Borowski E.

autor

Milewski S.

Bibliografia

• 1. Borowski, E. (2000) Novel approaches in the rational design of antifungal agents of low toxicity. Farmaco. 55, 206-208.
• 2.Zalkin, H. & Smith, J.L. (1998) Enzymes utilizing glutaminę as an amide donor. Adv. Enzymol. Relat. Areas Mol. Biol. 72, 87-145.
• 3.Milewski, S., Chmara, H., Andruszkiewicz, R. Borowski, E. (1985) Synthetic derivatives of A/3-fumaroyl-L-2,3- diaminopropanoic acid inactivate glucosamine synthetase from Candida albicans. Biochim. Biophys. Acta. 828, 247-254.
• 4.Zgodka, D., Milewski, S. & Borowski, E. (2001) A diffusible analogue of N3-(4-methoxyfumaroyl)-L-2,3- diaminopropanoic acid with antifungal activity. Microbiology (U.K.). 147, 1955-1959.
• 5.Andruszkiewicz, R., Milewski, S., Zieniawa, T. & Borowski, E. (1990) Anticandidal properties of N3-(4- methoxyfumaroyl)-L-2,3-diaminopropanoic acid oligopeptides. J. Med. Chem. 33 132-135.
• 6.Milewski, S., Andruszkiewicz, R., Zieniawa, T., Chmara, H. & Borowski, E. (1989) Rational design of FMDP- tripeptides, a new group of antifungal agents. Proc. 16th International Congress ofChemotherapy, Jerusalem, Israel, p. 540 (1-2).
• 7.Kasprzak, L., Milewski, S., Gumieniak, J. & Borowski, E. (1992) The influence of serum proteins on biological activity of anticandidal peptides containing N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid. J. Chemother. 4, 88-94.
• 8.Milewski, S., Andruszkiewicz, R. & Borowski, E. (1988) Substrate specificity of peptide permeases in Candida albicans. FEMS Microbiol Lett. 50, 73-78.
• 9.Payne, J. (1986) Drug delivery systems: Optimizing the structure of peptide carriers for synthetic antimicrobial drugs. Drugs Exp. Clin. Res. 12, 585-594.
• 10.Badet-Denisot, M.-A., Leriche, C., Massiere, F. & Badet, B. (1995) Nitrogen transfer in E. coli glucosamine-6P synthase. Investigations using substrate and bisubstrate analogs. Bioorg. Med. Chem. Lett. 5, 815-820.
• 11.Polak, A. (1988) Combinational therapy with antifungal drugs. Mycoses. 31(Suppl. 2), 45-53.
• 12.Beggs, W.H. (1986) Mechanism of synergistic interactions between amphotericin B and flucytosine. J. Antimicrob. Chemother. 17, 402-404.
• 13.Siler-Marinkovic, S., Mojovic, L., Davinic, V. & Bugarski, B. (1997) Liposomes as carriers of antimicrobial drugs. Drug. Dev. Industr. Pharm. 23, 483-488.
• 14. Brajtburg, J. & Bolard, J. (1996) Carrier effects on biological activity of amphotericin B. Clin. Microbiol. Rev. 9, 512 -531.
• 15.National Committee for Clinical Laboratory Standards (1997) Reference method for broth dilution antifungal susceptibility testing for yeast: Proposed standards. Document M27-A. National Committee for Clinical Laboratory Standards. Wayne, PA.
• 16.Milewski, S., Kuszczak, D., Jedrzejczak, R., Smith, R.J., Brown, A.J.P. & Gooday, GW. (1999) Oligomeric structure and regulation of Candida albicans glucosamine-6-phosphate synthase. J. Biol. Chem. 274, 4000-4008.
• 17.Kenig, M., Vandamme, E. & Abraham, E.P. (1976) The mode of action of bacilysin and anticapsin and biochemical properties of bacilysin-resistant mutants. J. Gen. Microbiol. 94, 46-54.
• 18.Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding. Anal. Biochem. 72, 248-254.
• 19.Kucharczyk, N., Denisot, M.-A., Le Goffic, F. & Badet, B. (1990) Glucosamine-6-phosphate synthase from Escherichia coli: Determination of the mechanism of inactivation by N3-fumaroyl-L-2,3-diaminopropionic derivatives. Biochemistry. 29, 3668-3676.
• 20.Bolard, J. (1986) How do the polyene macrolide antibiotics affect the cellular membrane properties. Biochim. Biophys. Acta. 864, 257-304.
• 21.Grzybowska, J., Sowinski, P., Gumieniak, J., Zieniawa, T. & Borowski, E. (1997) N-methyl- N-D- fructopyranosylamphotericin B methyl ester, new amphotericin B derivative of low toxicity. J. Antibiot. 50, 709-711.
• 22.Neuman,M. (1980) Basic mechanisms of antibiotic synergistic activity. Drugs Exptl. Clin. Res. 6, 259-264.
• 23.Milewski,S., Mignini, F. & Borowski, E. (1991) Synergistic action of Nikkomycin X/Z with azole antifungals on Candida albicans. J. Gen. Microbiol. 137, 2155-2161.