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

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.

Graphical abstractN-Alkylation of d-glucosaminitol-6P affords compounds that inhibit Candida albicans glucosamine-6P synthase and exhibit antifungal activity (MIC = 0.08 − 0.625 mg mL−1).Figure optionsDownload full-size imageDownload as PowerPoint slide