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

L D Jennings; Z Wawrzak; D Amorose; R S Schwartz; D B Jordan

doi:10.1016/s0960-894x(99)00424-2

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

Bioorg Med Chem Lett. 1999 Sep 6;9(17):2509-14. doi: 10.1016/s0960-894x(99)00424-2.

Authors

L D Jennings¹, Z Wawrzak, D Amorose, R S Schwartz, D B Jordan

Affiliation

¹ Dupont Agricultural Products, Stine Haskell Research Center, Newark, DE 19714, USA.

PMID: 10498198
DOI: 10.1016/s0960-894x(99)00424-2

Abstract

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.

MeSH terms

Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Hydro-Lyases / antagonists & inhibitors
Hydro-Lyases / chemistry
Hydro-Lyases / metabolism
Magnaporthe / drug effects*
Magnaporthe / enzymology
Magnaporthe / metabolism
Melanins / antagonists & inhibitors*
Melanins / biosynthesis
Models, Molecular

Substances

Enzyme Inhibitors
Melanins
Hydro-Lyases
scytalone dehydratase