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 0.08-0.625mgmL(-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.
Melcer
Anna
A
Department of Chemistry, University of Gdańsk, 18 Sobieskiego Street, 80-952 Gdańsk, Poland.
Łacka
Izabela
I
Gabriel
Iwona
I
Wojciechowski
Marek
M
Liberek
Beata
B
Wiśniewski
Andrzej
A
Milewski
Sławomir
S
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors; D006801:Humans; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; C020862:2-amino-2-deoxyglucitol; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D005944:Glucosamine