Phytoene desaturase inhibition by O-(2-phenoxy)ethyl-N-aralkylcarbamates.
O-[1-Ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-benzylcarbamate exhibits a marked inhibition of carotenoid biosynthesis. Forty-one analogues were synthesized and assayed for plant-type phytoene desaturase (PDS) and zeta-carotene desaturase (ZDS) inhibition in a cell-free system using recombinant enzymes obtained from Escherichia coli transformants. The target enzyme of all carbamates synthesized in this study is PDS and not ZDS; no inhibition of ZDS was observed using a 10(-4) M inhibitor concentration. Four compounds, O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-phenylethyl)carbamate (23), O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-chlorobenzyl)carbamate (25), O-[1-ethyl-2-(3-trifluoromethylphenoxy)]ethyl-N-(2-chlorobenzyl)carbamate (26), and O-[1-methyl-2-(3-trifluoromethylphenoxy)]ethyl-N-benzylcarbamate (30), were the most potent PDS inhibitors. Their pI(50) values, the negative logarithms of the molar concentration that produces a 50% inhibition, were 7.5, representing the same inhibitory activity as norflurazon. With respect to a structure-activity relationship the oxygen atom of the phenoxy group and a carbamate structure in O-(1-ethyl-2-phenoxy)ethyl-N-aralkylcarbamates studied were found to be essential for strong PDS inhibitors. Also, introduction of an ethyl group at the alpha-position of the ethylene bridge between the phenoxy group and the carbamate was important for a strong PDS inhibitor. Substituents at the 2- and/or 3-position of the phenoxybenzene ring were found to be favorable to a strong PDS inhibition of the analogues.
Ohki
Shinpei
S
Lehrstuhl für Physiologie und Biochemie der Pflanzen, Universität Konstanz, D-78457 Konstanz, Germany.
Miller-Sulger
Roswitha
R
Wakabayashi
Ko
K
Pfleiderer
Wolfgang
W
Böger
Peter
P
D002219:Carbamates / Q000032:analysis* / Q000494:pharmacology; D002338:Carotenoids / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000494:pharmacology; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
D002219:Carbamates; D004791:Enzyme Inhibitors; C474494:O-(1-Ethyl-2-(3-trifluoromethylphenoxy))ethyl-N-benzylcarbamate; D011724:Pyridazines; D011994:Recombinant Proteins; D002338:Carotenoids; D010088:Oxidoreductases; C022398:phytoene dehydrogenase; C099215:zeta-carotene desaturase; C008677:norflurazone