Inhibitory effects on mitochondrial complex I of semisynthetic mono-Tetrahydrofuran acetogenin derivatives

2003 ◽  
Vol 13 (22) ◽  
pp. 4101-4105 ◽  
Author(s):  
José R Tormo ◽  
Teresa Gallardo ◽  
Eva Peris ◽  
Almudena Bermejo ◽  
Nuria Cabedo ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Inhibitory Effects

Chemical Modification of the Mitochondrial Complex I Inhibitor 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline: Synthesis and Evaluation of N-Alkanoyl Derivatives

2000 ◽  
Vol 55 (7-8) ◽  
pp. 620-630 ◽  
Author(s):  
Gerhard Bringmann ◽  
Doris Feineis ◽  
Ralf God ◽  
Ralph Brückner ◽  
Jens Achim-Protzen ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Inhibitory Effects ◽  
Trichloromethyl Group ◽  
Hydrophobic Portion ◽  
Complex I Activity ◽  
Mitochondrial Complex I Inhibitor ◽  
Lipophilic Character

Abstract Several N-alkanoyl derivatives (4-9 and 13-16) of the potent mitochondrial complex I inhibitor TaClo (1-trichlorom ethyl-1,2,3,4-tetrahydro-β-carboline, 2) have been synthesized in order to elucidate the role of hydrophobic portion in the inhibitory action. Using rat brain homogenates or submitochondrial particles, the inhibitory effects of these compounds towards NADH-ubiquinone reductase (complex I) activity indeed appeared to correlate quite strongly with their lipophilic character. An X-ray structure analysis, exemplarily performed for N-acetyl-TaClo (4), revealed the N-substituent of such chlorinated agents to be dramatically pushed out of the β-carboline ring ‘plane’ due to the high steric demand of the huge trichloromethyl group at C-1.

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