Interactions between piperonyl butoxide analogues and metabolic enzymes conferring insecticide resistance
Author(s)
Philippou, Despina
Type
Thesis
Abstract
The insecticide synergist, piperonyl butoxide (PBO), has been used to reduce resistance
factors and to characterise metabolic resistance resulting from mixed function oxidases
(MFOs). Studies have also shown that PBO can interact with resistance-associated esterases.
It is well-documented that the mechanism by which PBO inhibits P450s is the interaction of
the methylenedioxyphenyl (MDP) moiety of PBO molecule with the haem moiety of the
enzyme. To investigate the interactions between PBO and esterases, a structure activity
relationship (SAR) study was carried out using analogues of PBO and E4, a resistanceassociated
esterase from the peach-potato aphid Myzus persicae. Results indicate that the
polyether and the alkyl chain were fundamentally important in this interaction. Removing one
oxygen atom from the MDP moiety of PBO did not affect the binding affinity, but increased
affinities resulted from the replacement of the polyether with an alkynyl ether chain or by
increasing the length of the alkyl chain.
An analogue, EN 16/5-1, that retains the ability to interact with esterases but loses the ability
to act on P450s, due to a modification to the MDP moiety, was used in conjunction with PBO
to facilitate characterisation of metabolic resistance in M. persicae and pollen beetle
Meligethes aeneus.
Selected analogues of PBO containing the alkynyl ether side chain exhibited high synergistic
effects in vivo and were found to be potent inhibitors of O-deethylation of 7-ethoxycoumarin
when tested against pyrethroid resistant M. aeneus.
The capability of some of the analogues to act as insecticide synergists was investigated in
vivo against two M. persicae clones possessing different metabolic resistance profiles.
Finally, the potential of PBO analogues to provide potent and/or specific synergism to
overcome insecticide resistance and reduce insecticide titre applied to crops is considered.
factors and to characterise metabolic resistance resulting from mixed function oxidases
(MFOs). Studies have also shown that PBO can interact with resistance-associated esterases.
It is well-documented that the mechanism by which PBO inhibits P450s is the interaction of
the methylenedioxyphenyl (MDP) moiety of PBO molecule with the haem moiety of the
enzyme. To investigate the interactions between PBO and esterases, a structure activity
relationship (SAR) study was carried out using analogues of PBO and E4, a resistanceassociated
esterase from the peach-potato aphid Myzus persicae. Results indicate that the
polyether and the alkyl chain were fundamentally important in this interaction. Removing one
oxygen atom from the MDP moiety of PBO did not affect the binding affinity, but increased
affinities resulted from the replacement of the polyether with an alkynyl ether chain or by
increasing the length of the alkyl chain.
An analogue, EN 16/5-1, that retains the ability to interact with esterases but loses the ability
to act on P450s, due to a modification to the MDP moiety, was used in conjunction with PBO
to facilitate characterisation of metabolic resistance in M. persicae and pollen beetle
Meligethes aeneus.
Selected analogues of PBO containing the alkynyl ether side chain exhibited high synergistic
effects in vivo and were found to be potent inhibitors of O-deethylation of 7-ethoxycoumarin
when tested against pyrethroid resistant M. aeneus.
The capability of some of the analogues to act as insecticide synergists was investigated in
vivo against two M. persicae clones possessing different metabolic resistance profiles.
Finally, the potential of PBO analogues to provide potent and/or specific synergism to
overcome insecticide resistance and reduce insecticide titre applied to crops is considered.
Date Issued
2010-06
Date Awarded
2010-08
Advisor
Wright, Denis
Moores, Graham
Sponsor
Endura SpA
Creator
Philippou, Despina
Publisher Department
Biology
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)