Rational design of N-alkyl derivatives of 2-amino-2-deoxy-d-glucitol-6P as antifungal agents

Anna Melcer; Izabela Łacka; Iwona Gabriel; Marek Wojciechowski; Beata Liberek; Andrzej Wiśniewski; Sławomir Milewski

doi:10.1016/j.bmcl.2007.09.072

Rational design of N-alkyl derivatives of 2-amino-2-deoxy-d-glucitol-6P as antifungal agents

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6602-6. doi: 10.1016/j.bmcl.2007.09.072. Epub 2007 Sep 25.

Authors

Anna Melcer¹, Izabela Łacka, Iwona Gabriel, Marek Wojciechowski, Beata Liberek, Andrzej Wiśniewski, Sławomir Milewski

Affiliation

¹ Department of Chemistry, University of Gdańsk, 18 Sobieskiego Street, 80-952 Gdańsk, Poland.

PMID: 17920268
DOI: 10.1016/j.bmcl.2007.09.072

Abstract

N-Alkyl and N,N-dialkyl derivatives of 2-amino-2-deoxy-d-glucitol-6P (ADGP) were synthesized and found to inhibit growth of human pathogenic fungi (MICs in the 0.08-0.625mgmL(-1) range for the most active compounds). It was thus shown that N-alkylation of ADGP provides novel inhibitors of a fungal enzyme, glucosamine-6P synthase, exhibiting higher antifungal activity than the parent compound, due to the increased lipophilicity and better uptake by fungal cells.

Publication types

Comparative Study

MeSH terms

Antifungal Agents / chemical synthesis*
Antifungal Agents / pharmacology
Candida albicans / drug effects
Candida albicans / enzymology
Candida albicans / growth & development
Drug Design
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Glucosamine / analogs & derivatives*
Glucosamine / chemical synthesis
Glucosamine / pharmacology
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / antagonists & inhibitors
Humans
Microbial Sensitivity Tests
Saccharomyces cerevisiae / drug effects
Saccharomyces cerevisiae / growth & development

Substances

Antifungal Agents
Enzyme Inhibitors
2-amino-2-deoxyglucitol
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Glucosamine