A new potent inhibitor of fungal melanin biosynthesis identified through combinatorial chemistry

A new fungicide lead has been identified by in vitro screening of a focused combinatorial library. Amides (768) were synthesized in pools of four and assayed as inhibitors of scytalone dehydratase. Deconvolution of one of the most active pools led to the discovery of a potent inhibitor of the enzyme...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1999-09, Vol.9 (17), p.2509-2514
Main Authors: Jennings, Lee D., Wawrzak, Zdzislaw, Amorose, Denise, Schwartz, Rand S., Jordan, Douglas B.
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Biological and medical sciences
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Hydro-Lyases - antagonists & inhibitors
Hydro-Lyases - chemistry
Hydro-Lyases - metabolism
Magnaporthe - drug effects
Magnaporthe - enzymology
Magnaporthe - metabolism
Medical sciences
Melanins - antagonists & inhibitors
Melanins - biosynthesis
Models, Molecular
Pharmacology. Drug treatments
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Summary:A new fungicide lead has been identified by in vitro screening of a focused combinatorial library. Amides (768) were synthesized in pools of four and assayed as inhibitors of scytalone dehydratase. Deconvolution of one of the most active pools led to the discovery of a potent inhibitor of the enzyme 3b (K i = 26 pM), which has fungicidal properties.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(99)00424-2