Reference

Kinetic properties of the inhibition of juvenile hormone esterase by two trifluoromethyl ketones and O-ethyl S-phenyl phosphoramidothioate

Kinetic properties of the inhibition of juvenile hormone esterase by two trifluoromethyl ketones and O-ethyl S-phenyl phosphoramidothioate. Abdel-Aal, Yehia A. I.; Roe, Richard M.; Hammock, Bruce D. (Dep. Entomol., Univ.Chemicals with cas numbers 41577-03-1 and 26944-42-3 also play role. California, Davis, CA 95616, USA). Pestic. Biochem. Physiol., 21(2), 232-41 (English) 1984. CODEN: PCBPBS. ISSN: 0048-3575. DOCUMENT TYPE: Journal CA Section: 5 (Agrochemical Bioregulators) Section cross-reference(s): 12 Some inhibition kinetic properties and in vivo inhibition of the plasma juvenile hormone esterase [9013-79-0] from the cabbage looper (Trichoplusia ni) by 1 phosphoramidothioate and 2 trifluoromethyl ketones were examd. O-Et S-Ph phosphoramidothioate (I) [41577-03-1] reacted irreversibly with the enzyme in a time-dependent manner, and the inhibition reaction can be factored into a reversible step with a dissocn. const., Kd, of 4.55 ′ 10-5M, followed by a phosphorylation step with a rate const., k2, of 1.98/min. The phosphorylated enzyme did not show spontaneous recovery after 48 h of dialysis. On the other hand, the 2 trifluoromethyl ketones acted as reversible inhibitors, as the inhibited enzyme was regenerated completely after dialysis. However, 1,1,1-trifluoro-3-octylthiopropan-2-one [89820-00-8], in contrast to 1,1,1-trifluorotetradecan-2-one [26944-42-3], showed progressive time-dependent inhibition, and its reaction with the enzyme followed characteristic bimol. 2nd-order kinetics with a rate const., ki, of 3.37 ′ 107M-1/min. The in vivo inhibition data of topically-treated larvae at equimolar amts. of the tested compds. indicated rapid penetration, and the stability of the inhibition was higher for I than for the trifluoromethyl ketones. The interactions between juvenile hormone and juvenile hormone esterase is discussed. .

Substituted thiotrifluoropropanones as potent selective inhibitors of juvenile hormone esterase

Substituted thiotrifluoropropanones as potent selective inhibitors of juvenile hormone esterase. Hammock, Bruce D.; Abdel-Aal, Yehia A. I.; Mullin, Christopher A.; Hanzlik, Terry N.; Roe, Richard M. (Dep. Entomol., Univ. California, Davis, CA 95616, USA). Pestic. Biochem. Physiol., 22(2), 209-23 (English) 1984. CODEN: PCBPBS. ISSN: 0048-3575. DOCUMENT TYPE: Journal CA Section: 5 (Agrochemical Bioregulators) Section cross-reference(s): 12 A series of 27 substituted thio-1,1,1-trifluoropropanones was synthesized by reacting the corresponding thiol with 1,1,1-trifluoro-3-bromopropanone [431-35-6]. The resulting sulfides were screened as inhibitors of hemolymph juvenile hormone esterase (JH esterase) [50812-15-2] and a-naphthyl acetate esterase [9013-79-0] activity of the cabbage looper, Trichoplusia ni, elec. eel acetylcholinesterase [9000-81-1], bovine trypsin [9002-07-7], and bovine a-chymotrypsin [9004-07-3]. The presence of the sulfide bond increased the inhibitory potency on all of the enzymes tested when compared with compds. lacking the sulfide. In general, the compds. were poor inhibitors of chymotrypsin and moderate inhibitors of trypsin. By varying the substituent on the sulfide, good inhibitory activity was obtained on a-naphthyl acetate esterase, acetylcholinesterase, while some of the compds. were extremely powerful inhibitors of juvenile hormone esterase. 92682-28-5 which is the cas registry number is also used here. The most powerful inhibitor tested was 3-octylthio-1,1,1-trifluoro-2-propanone [89820-00-8], with an I50 of 2.3 ′ 10-9M on JH esterase. This compd. showed a molar refractivity similar to that of the JH II backbone, was not toxic to T. ni, and was moderately toxic to mice, with a 48-h LD50 of >750 mg/kg. It effectively delayed pupation when applied to pre-wandering larvae of T. ni, as expected for a JH esterase inhibitor. Thus, some members of this series are promising for evaluating the role of JH esterase in insect development. The series also indicates that, by varying the substituent on the sulfide moiety, potent transition-state inhibitors can be developed for a wide variety of esterases and proteases. .