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 3b (K(i) = 26 pM), which has fungicidal properties.
Jennings
L D
LD
Dupont Agricultural Products, Stine Haskell Research Center, Newark, DE 19714, USA.
Wawrzak
Z
Z
Amorose
D
D
Schwartz
R S
RS
Jordan
D B
DB
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D020082:Magnaporthe / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008958:Models, Molecular
D004791:Enzyme Inhibitors; D008543:Melanins; D006836:Hydro-Lyases; C082741:scytalone dehydratase