title: Development of multifunctional metabolic synergists to suppress the evolution of resistance against pyrethroids in insects that blood feed on humans.
abstract: BACKGROUND
  Pyrethroids are the insecticides of choice when exposure to humans is likely, such as occurs in vector and public-health-related control programs. Unfortunately, the pyrethroids share a common resistance mechanism with dichlorodiphenyltrichloroethane (DDT), knockdown resistance (kdr), and prior extensive use of DDT has predisposed the pyrethroids to cross-resistance via kdr. Given the widespread occurrence of kdr, the use of synergists with pyrethroids is considered to be prudent to guard against the selection of multiply resistant insects.
  
  
  RESULTS
  3-Phenoxybenzyl hexanoate (PBH) was synthesized as a multifunctional pyrethroid synergist that, besides being a surrogate substrate for sequestration/hydrolytic carboxylesterases, now also functions as a substrate for oxidative xenobiotic metabolism. The addition of PBH to permethrin-treated females of the ISOP450 strain of Culex pipiens quinquefasciatus resulted in a threefold increase in synergism, as judged by the synergistic ratio. Similarly, PBH synergized the action of deltamethrin sixfold on females of the common bed bug, Cimex lectularius, and was 2.8-fold more synergistic than piperonyl butoxide (PBO).
  
  
  CONCLUSIONS
  PBH synergized the action of both type I and type II pyrethroids in a mosquito vector (Cx. p. quinquefasciatus) and in a public-health pest, C. lectularius, respectively, indicating a broad spectrum of action on blood-feeding insects. PBH appears to have residual properties similar to permethrin and is itself non-toxic, unlike PBO, and therefore should be compatible with existing pyrethroid formulations used for insecticide-treated nets and home/residential sprays.
authors.affiliation: Department of Entomology, Comstock Hall, Cornell University, Ithaca, NY, USA.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Hardstone
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Strycharz
authors.forename: Junheon
authors.initials: J
authors.lastname: Kim
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Park
authors.forename: Kyong Sup
authors.initials: KS
authors.lastname: Yoon
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Ahn
authors.forename: Laura C
authors.initials: LC
authors.lastname: Harrington
authors.forename: Si Hyeock
authors.initials: SH
authors.lastname: Lee
authors.forename: J Marshall
authors.initials: JM
authors.lastname: Clark
mesh_terms: D000818:Animals; D001511:Bedbugs / Q000187:drug effects*; D002208:Caproates / Q000138:chemical synthesis* / Q000494:pharmacology*; D003465:Culex / Q000187:drug effects*; D005260:Female; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D026023:Permethrin / Q000494:pharmacology*; D010574:Pesticide Synergists / Q000494:pharmacology*; D010882:Piperonyl Butoxide / Q000494:pharmacology*; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: C000606085:3-phenoxybenzyl hexanoate; D002208:Caproates; D007306:Insecticides; D009570:Nitriles; D010574:Pesticide Synergists; D011722:Pyrethrins; C017180:decamethrin; D026023:Permethrin; D010882:Piperonyl Butoxide
keywords: 3-phenoxybenzyl hexanoate; Cimex lectularius; Culex pipiens quinquefasciatus; deltamethrin; permethrin; synergist