Bc. Black et al., INSECTICIDAL ACTION AND MITOCHONDRIAL UNCOUPLING ACTIVITY OF AC-303,630 AND RELATED HALOGENATED PYRROLES, Pesticide biochemistry and physiology, 50(2), 1994, pp. 115-128
The mode of action of the experimental insecticide/acaricide, AC-303,6
30 ethyl)-5-(trifluoromethyl)pyrrole-3-carbonitrile); Pirate, Stalker,
CAS No. [122453-73-0]), and its halogenated pyrrole analogs was studi
ed. AC-303,630 caused greatly increased respiratory activity in German
cockroaches but was virtually inactive as an uncoupler against isolat
ed mitochondria. However, its N-dealkylated analog, AC-303,268, was a
potent uncoupler with notable activity in the range of 10-100 nM again
st rat, fish, and insect mitochondria. Both respiratory stimulation an
d toxicity were antagonized in insects by pretreatment with the monoox
ygenase inhibitor piperonyl butoxide. Structure-activity studies with
a range of halogenated pyrroles also supported a relationship between
uncoupling and toxicity. Based on these results it is concluded that A
C-303,630 is a propesticide that is activated by the oxidative removal
of the N-ethoxymethyl group. This releases a lipophilic, weakly acidi
c pyrrole metabolite which exerts its toxicity through mitochondrial u
ncoupling. (C) 1994 Academic Press, Inc.