title: Structure-activity relationship study of trifluoromethylketones: inhibitors of insect juvenile hormone esterase.
abstract: The juvenile hormone esterase (JHE) regulates juvenile hormone titre in insect hemolymph during its larval development. It has been suggested that JHE could be targeted for use in insect control. This enzyme can also be considered as involved in the phenomenon of endocrine disruption by xenobiotics in beneficial insects. Consequently, there is a need to know the characteristics of the molecules able to act on the JHE. Trifluoromethylketones (TFKs) are the most potent JHE inhibitors found to date and different quantitative structure-activity relationships (QSARs) have been derived for this group of chemicals. In this context, a set of 181 TFKs (118 active and 63 inactive compounds), tested on Trichoplusia ni for their JHE inhibition activity and described by physico-chemical descriptors, was split into different training and test sets to derive structure-activity relationship (SAR) models from support vector classification (SVC). A SVC model including 88 descriptors and derived from a Gaussian kernel was selected for its predictive performances. Another model computed only with 13 descriptors was also selected due to its mechanistic interpretability. This study clearly illustrates the difficulty in capturing the essential structural characteristics of the TFKs explaining their JHE inhibitory activity.
authors.affiliation: ITODYS, UMR 7086, Université Paris 7, Paris, France. doucet@univ-paris-diderot.fr
authors.forename: J P
authors.initials: JP
authors.lastname: Doucet
authors.forename: A
authors.initials: A
authors.lastname: Doucet-Panaye
authors.forename: J
authors.initials: J
authors.lastname: Devillers
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000494:pharmacology*; D007915:Lepidoptera / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006845:Hydrocarbons, Fluorinated; D002265:Carboxylic Ester Hydrolases; C038003:juvenile hormone esterase