Synthetic atpenin analogs: Potent mitochondrial inhibitors of mammalian and fungal succinate-ubiquinone oxidoreductase.
Atpenins and harzianopyridone represent a unique class of penta-substituted pyridine-based natural products that are potent inhibitors of complex II (succinate-ubiquinone oxidoreductase) in the mitochondrial respiratory chain. These compounds block electron transfer in oxidative phosphorylation by inhibiting oxidation of succinate to fumarate and the coupled reduction of ubiquinone to ubiquinol. From our investigations of complex II inhibitors as potential agricultural fungicides, we report here on the synthesis and complex II inhibition for a series of synthetic atpenin analogs against both mammalian and fungal forms of the enzyme. Synthetic atpenin 2e provided optimum mammalian and fungal inhibition with slightly higher potency than natural occurring atpenin A5.
Selby
Thomas P
TP
DuPont Crop Protection, Stine-Haskell Research Center, 1094 Elkton Road, Newark, DE 19711, USA. thomas.p.selby@usa.dupont.com
Hughes
Kenneth A
KA
Rauh
James J
JJ
Hanna
Wayne S
WS
D000818:Animals; D002417:Cattle; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005658:Fungi / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology*; D010085:Oxidative Phosphorylation; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011725:Pyridines; D011728:Pyridones; C058278:atpenin A5; D042963:Electron Transport Complex II