The thiourea insecticide/acaricide diafenthiuron has a novel mode of action: inhibition of mitochondrial respiration by its carbodiimide product
1991
Ruder, F.J. | Guyer, W. | Benson, J.A. | Kayser, H.
The thiourea diafenthiuron (CGA 106630) is a novel insecticide/acaricide. The present paper is concerned with the molecular mechanism underlying its action. So far, we have not found any direct target for diafenthiuron itself to explain its toxic effect. Since it is known that diafenthiuron is rapidly desulfurated abiotically to the pesticidal carbodiimide CGA 140408 in the presence of sunlight and singlet oxygen, CGA 140408 is probably the toxic agent mediating the in vivo action of diafenthiuron. Indeed, CGA 140,408 is one of the major in vivo products of diafenthiuron in Calliphora. Furthermore, there is evidence that cytochrome P450 mediates this desulfuration, biotically, since diaifenthiuron binds to cytochrome P450 as a substrate in rat liver microsomes. None of the known molecular targets of current commercial insecticides are affected by either diafenthiuron or CGA 140408 (e.g., acetylcholinesterase, sodium channel, acetylcholine receptor, chitin synthesis). Further, we cannot confirm a proposed octopaminergic action of CGA 140408. However, we have been able to demonstrate that CGA 140408, but not diafenthiuron, is a potent in vitro inhibitor of mitochondrial respiration in rat liver and Calliphora flight muscles. It selectively blocks the coupling site in a time-dependent manner which is different from the action of other pesticides. The resemblance in the chemical structure to the well-known mitochondrial inhibitor dicyclohexylcarbodiimide suggests that CGA 140408 inhibits mitochondrial ATPase. Further experimental details are reported in a forthcoming paper.
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