Antifungal peptides with novel specific inhibitors of glucosamine 6-phosphate synthase.

Abstract

N3-4-Methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP) has been found to be a strong and selective inhibitor of glucosamine 6-phosphate synthase from Candida albicans. Incorporation of FMDP into a dipeptide structure has produced effective antifungal agents (portage transport). A number of dipeptides containing FMDP have been synthesized, with Nva-FMDP showing the highest in vitro activity against different fungi, including Candida albicans (MIC90 = 2.2 micrograms/ml for 50 clinical strains), Cryptococcus neoformans and Aspergillus spp. This compound, when tested in a general candidiosis model infection in mice, gave PD50/10 and CD50/10 values of 5.0 and 1.63 mg/kg, respectively. Meanwhile, the LD50 value after i.v. administration was higher than 300 mg/kg.

• Authors: S Milewski, H Chmara, R Andruszkiewicz, E Borowski, M Zaremba, J Borowski
• Journal: Drugs under experimental and clinical research (Drugs Exp Clin Res) Vol. 14 Issue 7 Pg. 461-5 ( 1988) ISSN: 0378-6501 [Print] Switzerland
• PMID: 3149235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Dipeptides
• Fumarates
• beta-Alanine
• N(3)-(4-methoxyfumaroyl)-2,3-diaminopropionic acid
• Transaminases
• Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
• Alanine

Topics

• Alanine (analogs & derivatives)
• Antifungal Agents (chemical synthesis)
• Candida (drug effects, isolation & purification)
• Dipeptides (chemical synthesis, pharmacology)
• Fumarates (chemical synthesis, pharmacology)
• Fungi (drug effects)
• Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) (antagonists & inhibitors)
• Humans
• Microbial Sensitivity Tests
• Structure-Activity Relationship
• Transaminases (antagonists & inhibitors)
• beta-Alanine (analogs & derivatives, chemical synthesis, pharmacology)