RESUMO
The synthesis, chemical derivatization, and investigation of the inhibitory properties of novel cyclitol derivatives on the phosphatidylinositol 4-kinase enzymes PI4K55 and PI4K230 involved in the phosphatidylinositol cycle are reported. Some of the prepared cyclitol derivatives (i.e. 9, 11, 12, and 14) proved to be very powerful and specific irreversible inhibitors of PI4K230 at or below a concentration of 1 mM.
Assuntos
Cicloexanonas/síntese química , Inibidores Enzimáticos/síntese química , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Álcoois Açúcares/síntese química , Animais , Bovinos , Cicloexanonas/química , Inibidores Enzimáticos/química , Isoenzimas/antagonistas & inibidores , Relação Estrutura-Atividade , Álcoois Açúcares/químicaAssuntos
Antibacterianos/síntese química , Carboidratos/química , Amino Açúcares/química , Aminoglicosídeos , Antibacterianos/farmacologia , Sequência de Carboidratos , Glicosilação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Estrutura MolecularRESUMO
Novel pseudodisaccharide-type aminocyclitol antibiotic models, built up from D-arabinose, D-ribose, D-glucosamine, L-ristosamine and L-acosamine have been synthesized by the glycosylation of suitably protected (azido)deoxyinosose aglycones derived by the Ferrier carbocyclic ring transformation of carbohydrate precursors. An alternative approach to related pseudodisaccharides, based on the Ferrier carbocyclization of reducing disaccharides, has also been elaborated. This latter method extends the scope of the Ferrier reaction, by demonstrating that acid-labile 2-deoxydisaccharides can also be readily transformed into the corresponding pseudodisaccharides under the slightly acidic conditions of this ring-transformation.
