Non-steroidal ecdysteroid agonist chromafenozide: Gene induction activity, cell proliferation inhibition and larvicidal activity

The activity profile of the most recent commercial non-steroidal ecdysteroid agonist chromafenozide (ANS-118), was evaluated on a comparative basis to methoxyfenozide (RH-2485) that is to date the most potent commercial agonist against Lepidoptera. This was done first at the molecular and cellular level regarding its induction activity of an ecdysteroid-responsive reporter gene and its cell proliferation inhibition activity, and subsequently at the level of larvicidal toxicity. For in vitro experiments three ecdysteroid-responsive insect cell lines were used: Drosophila melanogaster (Diptera) S2 cells, Bombyx mori (Lepidoptera) Bm5 cells and Spodoptera exigua (Lepidoptera) Se4 cells. The in vivo toxicity was scored against two major lepidopteran pests in the world, the beet armyworm S. exigua and the cotton leafworm Spodoptera littoralis. In vitro results revealed that chromafenozide and methoxyfenozide are highly potent against lepidopteran cells compared to dipteran cells, supporting the lepidopteran-specificity of these compounds. Interestingly, in the reporter gene induction experiments and proliferation inhibition experiments, a slightly higher efficacy was observed in S2 compared to Bm5 cells at high concentrations of chromafenozide and methoxyfenozide. Our analysis shows the high potency and efficacy of the chromafenozide compound as an ecdysteroid agonist towards lepidopteran insects at a level that is similar to methoxyfenozide.