title: The interactions of piperonyl butoxide and analogues with the metabolic enzymes FE4 and CYP6CY3 of the green peach aphid Myzus persicae (Hemiptera: Aphididae).
abstract: BACKGROUND
  Piperonyl butoxide (PBO) is a well-known insecticide synergist capable of interacting with phase 1 metabolic enzymes, specifically esterases and cytochrome P450s. In this study, structure-activity relationship analyses were used to characterise the interaction of around 30 analogues of PBO with the esterase FE4 and the P450 CYP6CY3 from insecticide-resistant Myzus persicae (Sulzer), in order to predict the synthesis of more potent inhibitors.
  
  
  RESULTS
  Enzyme inhibition studies were performed against esterase and oxidase activities and, together with in silico modelling, key activity determinants of the analogues were identified and optimised. Novel analogues were then designed and synthesised, some of which showed greater inhibition against both enzymatic systems: specifically, dihydrobenzofuran moieties containing an alkynyl side chain and a butyl side chain against FE4, and benzodioxole derivatives with a propyl/butyl side chain and an alkynyl ether moiety for CYP6CY3.
  
  
  CONCLUSIONS
  In vitro assays identified potential candidate synergists with high inhibitory potency. The in vivo confirmation of such results will allow consideration for a possible use in agriculture. © 2016 Society of Chemical Industry.
authors.affiliation: ApresLabs Ltd, Harpenden, Herts, UK.|Dipartimento di Scienze delle Produzioni Vegetali Sostenibili, Università Cattolica del Sacro Cuore, Piacenza, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Panini
authors.affiliation: Endura SpA, Ravenna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tozzi
authors.affiliation: Rothamsted Research, Harpenden, Herts, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Bass
authors.affiliation: Rothamsted Research, Harpenden, Herts, UK.
authors.forename: Christoph T
authors.initials: CT
authors.lastname: Zimmer
authors.affiliation: Rothamsted Research, Harpenden, Herts, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Field
authors.affiliation: Endura SpA, Ravenna, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Borzatta
authors.affiliation: Dipartimento di Scienze delle Produzioni Vegetali Sostenibili, Università Cattolica del Sacro Cuore, Piacenza, Italy.
authors.forename: Emanuele
authors.identifier: http://orcid.org/0000-0001-9845-6038
authors.initials: E
authors.lastname: Mazzoni
authors.affiliation: ApresLabs Ltd, Harpenden, Herts, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Moores
mesh_terms: D000818:Animals; D001042:Aphids / Q000201:enzymology*; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004950:Esterases / Q000037:antagonists & inhibitors; D007305:Insecticide Resistance; D010574:Pesticide Synergists / Q000737:chemistry; D010882:Piperonyl Butoxide / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D010574:Pesticide Synergists; D003577:Cytochrome P-450 Enzyme System; D004950:Esterases; D010882:Piperonyl Butoxide
keywords: Myzus persicae; P450s; esterase; piperonyl butoxide; structure-activity relationship; synergist