RESUMO
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.
Assuntos
Antifúngicos/síntese química , Glucosamina/análogos & derivados , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/enzimologia , Candida albicans/crescimento & desenvolvimento , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glucosamina/síntese química , Glucosamina/farmacologia , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/antagonistas & inibidores , Humanos , Testes de Sensibilidade Microbiana , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimentoRESUMO
Mono- and di-N-alkylated derivatives of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-beta-D-glucose (alkyl=methyl, ethyl, propyl, butyl, pentyl, hexyl, benzyl) were synthesised by the reductive alkylation of per-O-acetyl-d-glucosamine. (N-ethyl, N-propyl, N-butyl, N-pentyl and N-hexyl)-1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-beta-D-glucoses were deacetylated in order to attempt an enzymatic phosphorylation. All products were characterised by means of IR, NMR and MS spectra. N-Ethyl- and N-pentyl-d-glucosamines were found to exhibit weak antifungal activity.
Assuntos
Desoxiglucose/química , Glucosamina/análogos & derivados , Antifúngicos/farmacologia , Configuração de Carboidratos , Sequência de Carboidratos , Desoxiglucose/síntese química , Glucosamina/síntese química , Glucosamina/química , Glucosamina/farmacologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Químicos , Dados de Sequência Molecular , Fosforilação , Prótons , Espectrofotometria Infravermelho , TemperaturaRESUMO
The single-crystal X-ray diffraction and high-resolution 1H and 13C NMR spectral data for the title compound are reported. The influence of the ring oxygen atom on the J(1,2e) and J(4,5) coupling constants for 2-deoxy-D-lyxo- and -D-xylo-hexopyranosides is discussed.
