Abstract
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 [Na2Fe(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 (I50 = 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 (Ki = 3.2 × 10-9 M, Km 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 76-88 |
| Number of pages | 13 |
| Journal | Pesticide Biochemistry and Physiology |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1982 |
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ASJC Scopus subject areas
- Agronomy and Crop Science
- Biochemistry
- Physiology
Cite this
Trifluoromethylketones as possible transition state analog inhibitors of juvenile hormone esterase. / Hammock, Bruce D.; Wing, Keith D.; McLaughlin, James; Lovell, Victor M.; Sparks, Thomas C.
In: Pesticide Biochemistry and Physiology, Vol. 17, No. 1, 1982, p. 76-88.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Trifluoromethylketones as possible transition state analog inhibitors of juvenile hormone esterase
AU - Hammock, Bruce D.
AU - Wing, Keith D.
AU - McLaughlin, James
AU - Lovell, Victor M.
AU - Sparks, Thomas C.
PY - 1982
Y1 - 1982
N2 - 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 [Na2Fe(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 (I50 = 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 (Ki = 3.2 × 10-9 M, Km 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.
AB - 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 [Na2Fe(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 (I50 = 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 (Ki = 3.2 × 10-9 M, Km 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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UR - http://www.scopus.com/inward/citedby.url?scp=0020024514&partnerID=8YFLogxK
U2 - 10.1016/0048-3575(82)90128-6
DO - 10.1016/0048-3575(82)90128-6
M3 - Article
VL - 17
SP - 76
EP - 88
JO - Pesticide Biochemistry and Physiology
JF - Pesticide Biochemistry and Physiology
SN - 0048-3575
IS - 1
ER -