Insect Control: Biological and Synthetic Agents - Index of

Figure 4 Folded and extended conformations of fenvalerate.
common conformations (within 10 kcal/mol of the
ground energy) for the active isomers of pyrethrin I,
deltamethrin, and fenvalerate (representatives of
each of the three other main series of pyrethroids).
To define the bioactive conformer, they also considered
a further seven pyrethroid structures, both
active and inactive. Similarity/dissimilarity searches
using Cosine and Tanimoto coefficients together
with superimposition considerations indicated the
folded form as the common bioactive conformation
for all four types of pyrethroids.
For deltamethrin (a cyclopropane ester), this bioactive
folded conformation is close to minimum
energy, and is similar to that both of the crystal
structure and as observed in solution by NMR
(under certain conditions). However, for fenvalerate
(not containing a cyclopropane acid moiety), the extended
form (Figure 4) has lower minimum energy
than the bioactive folded conformation.
However, another recent study appears to contradict
the above findings. Using new computational
methodologies based on cluster analysis of
molecular dynamics trajectories, Ford et al. (2002)
proposed an ‘‘extended’’ conformation for the lethal
action of both Type I and Type II pyrethroids, which
would also account for the negative temperature
coefficient. For knockdown activity (Type I compounds
only), he proposed a different higher-energy
conformation which is not accessible to Type II pyrethroids.
Not being a minimum-energy conformation,
this would be transient in nature, and would occur
with a higher probability at elevated temperatures
(i.e., positive temperature correlation with knockdown
activity). Once again the key torsion angles,
T2 and T4, lie around the ester bond, T3 being invariant
throughout the dynamics simulations undertaken
in this study.
1.5. Resistance to Pyrethroids
1: Pyrethroids 13
Under selection from repeated sprays of insecticides,
individuals possessing biochemical mechanisms that
can detoxify the insecticide more rapidly or are less
sensitive to it are likely to be favoured. These resistant
insects survive doses that would kill normally
sensitive individuals. Genes encoding these mechanisms
will then be passed on to the succeeding generations,
resulting in pest populations that are not
controlled effectively. This can lead to farmers increasing
the rate or frequency of applications,
imposing further selection pressure and ultimately
leading to a situation whereby the pests become
totally immune. Removal of selection pressure may
result in the pest populations regaining some degree
of sensitivity, particularly if there is a fitness cost to
resistance such as longer development times or reduced
over-wintering ability. Usually, however, the
population never regains the degree of sensitivity of
the naïve population, and often there appears to be
little fitness cost so that high numbers of resistant
pests remain in the population. Pesticide resistance
has occurred with all insecticides; the existence
of resistance mechanisms common to pyrethroids
and other older insecticides meant that onset of
resistance to the new compounds was quite rapid.
Many factors, in particular the type of crop and
the history of insecticide use, can affect the selection
and dominance of resistance mechanism(s) within
an insect species. In addition, the relative importance
of these mechanisms can change over time
(Gunning et al., 1991). Thus, management of resistance
requires knowledge of the mechanism(s)
present and ideally also their relative contribution.
Though the nature of the resistance mechanisms can
be identified relatively straightforwardly, there are,
as yet, no established methods for predicting their
relative importance in field strains of resistant
insects. Such prediction requires a multidisciplinary
approach based on both in vivo and in vitro
assays. The concept of using novel selective inhibitors,
designed using structure–activity investigations
and ideally devoid of insecticidal activity, could
prove particularly useful in determining the biochemical
mechanism(s) responsible for resistance.
The design of such inhibitors will need to take
into consideration the variations in specificities of