Trifluoromethylketones as possible transition state analog inhibitors of juvenile hormone esterase
A series of compounds containing the trifluoromethylketone group have been synthesized utilizing either a modified Grignard procedure or by reacting selected aliphatic bromides or tosylates with the Collman reagent [Na 2Fe(CO) 4]. When tested in vitro as inhibitors of crude juvenile hormone esterase...
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Published in | Pesticide biochemistry and physiology Vol. 17; no. 1; pp. 76 - 88 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
01.01.1982
|
Subjects | |
Online Access | Get full text |
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Summary: | A series of compounds containing the trifluoromethylketone group have been synthesized utilizing either a modified Grignard procedure or by reacting selected aliphatic bromides or tosylates with the Collman reagent [Na
2Fe(CO)
4]. When tested
in vitro as inhibitors of crude juvenile hormone esterase from the hemolymph of the cabbage looper,
Trichoplusia ni (Noctuidae), the most active compounds were trifluoromethylketones possessing either a juvenoid-like structure or a straight aliphatic chain. The logarithm of the inhibitory potency of the aliphatic compounds was proportional to their chain length, up to 1,1,1-trifluorotetradecan-2-one (I
50 = 1 × 10
−7
M). This powerful inhibition was found to be highly selective for JHE, reversible, competitive by Lineweaver-Burk analysis, and was characterized by high affinity of the inhibitor for the esterase (
K
i
= 3.2 × 10
−9
M,
K
m
JH III = 2 × 10
−7
M). Other trifluoromethylketones were shown to be inhibitors of
T. ni α-naphthylacetate esterase and bovine trypsin. By analogy with the mechanism of trypsin action, trifluoromethylketones are probably potent inhibitors due to their resemblance to a tetrahedral transition state on the reaction coordinate to the acylated enzyme. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0048-3575 1095-9939 |
DOI: | 10.1016/0048-3575(82)90128-6 |