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

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 0.08–0.625 mg mL −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.