Synthesis and characterization of Deltalac-acetogenins that potently inhibit mitochondrial complex I.
Four Deltalac-acetogenins have been prepared and characterized as inhibitors of the mitochondrial respiratory chain, to define the effects of unsaturation within the alkyl substituents. In keeping with earlier reports, the presence of acetylenic functionalities within the alkyl substituents slightly diminished their potency of inhibition of NADH oxidase activity, which measures the overall transfer of electrons from NADH to oxygen through mitochondrial complexes I, III, and IV. In contrast, both of the acetylenic Deltalac-acetogenins were far more active in a NADH-ubiquinone Q(1) oxidoreductase assay that measures complex I function per se.
Chapuis
Jean-Charles
JC
Center for BioEnergetics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Khdour
Omar
O
Cai
Xiaoqing
X
Lu
Jun
J
Hecht
Sidney M
SM
D054378:Acetogenins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008929:Mitochondria, Heart / Q000201:enzymology; D021241:Spectrometry, Mass, Electrospray Ionization
D054378:Acetogenins; D004791:Enzyme Inhibitors; D042967:Electron Transport Complex I