Synthesis and antifungal properties of compounds which target the alpha-aminoadipate pathway.
Fungi synthesize lysine via the alpha-aminoadipate pathway, which is not found in plants or animals. This pathway has been proposed as a target for antifungal agents, but until now no reports have appeared to test this proposal. Hampering studies on the susceptibility of filamentous fungi such as those of the clinically important genus Aspergillus is the fact that growth quantitation is notoriously difficult. We have used the recently-reported XTT-based method of biomass quantitation to measure the susceptibility of Aspergillus nidulans strain A28 to growth suppression by novel compounds designed to target early steps in the alpha-aminoadipate lysine biosynthesis pathway, specifically those steps involving (R)-homocitrate and (2R,3S)-homoisocitrate. Three compounds show moderate inhibition of fungal growth, which can be partially restored by the presence of lysine in the growth medium.
Palmer
D R J
DR
Department of Chemistry, University of Saskatchewan, Saskatoon, Canada.
Balogh
H
H
Ma
G
G
Zhou
X
X
Marko
M
M
Kaminskyj
S G W
SG
Kaminskyj
S G
SG
D015074:2-Aminoadipic Acid / Q000378:metabolism*; D000478:Alkylation; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001233:Aspergillus nidulans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D018533:Biomass; D002951:Citrates / Q000378:metabolism; D003470:Culture Media; D007202:Indicators and Reagents; D008239:Lysine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism
D000935:Antifungal Agents; D002951:Citrates; D003470:Culture Media; D007202:Indicators and Reagents; D015074:2-Aminoadipic Acid; D008239:Lysine