Function of the alkyl side chains of Deltalac-acetogenins in the inhibitory effect on mitochondrial complex I (NADH-ubiquinone oxidoreductase).
We synthesized a series of Deltalac-acetogenins in which the two alkyl side chains were systematically modified, and examined their inhibitory effect on bovine heart mitochondrial complex I (NADH-ubiquinone oxidoreductase). The results revealed that the physicochemical properties of the side chains, such as the balance of hydrophobicity and the width (or bulkiness) of the chains, are important structural factors for a potent inhibitory effect of amphiphilic Deltalac-acetogenins. This is probably because such properties decide the precise location of the hydrophilic bis-THF ring moiety in the enzyme embedded in the inner mitochondrial membrane.
Ichimaru
Naoya
N
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Abe
Masato
M
Murai
Masatoshi
M
Senoh
Mai
M
Nishioka
Takaaki
T
Miyoshi
Hideto
H
D054378:Acetogenins; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D054378:Acetogenins; D004791:Enzyme Inhibitors; D005233:Fatty Alcohols; D007783:Lactones; D042967:Electron Transport Complex I