Structure-activity analysis of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters as inhibitors of the NADH:ubiquinone oxidoreductase (complex I).
The structural and electronic properties of fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters were studied and related to the inhibitory effects on NADH:ubiquinone oxidoreductase (complex I). Electrostatic potential surfaces, dipole moments and molecular geometries were analysed. Based on the conformational analysis and the electronic parameters, a simple model for the active site of the fluorinated 1-N-arylamino-1-arylmethanephosphonic acid esters was developed, explaining the inhibitory power. The strongest inhibition effects were found for the 1-(N-4-trifluoromethoxyphenyl)-amino-1-phenylmethanephosphonic acid diethyl ester 1bab.
Dronia
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Institut für Anorganische Chemie und Strukturchemia I, Heinrich-Heine-Universität Düsseldorf, Germany.
Gruss
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Hägele
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Friedrich
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Weiss
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H
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D010101:Oxygen Consumption; D011487:Protein Conformation; D012984:Software; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D016660:NAD(P)H Dehydrogenase (Quinone)