ACC inhibitors(Nanjing Sanhome Pharmaceutical)

Traditional management of Conogethes punctiferalis is challenged by larval boring behavior limiting insecticide contact. This study demonstrates a novel application of spirotetramat, an acetyl-CoA carboxylase (ACC) inhibitor typically targeting sucking pests, to disrupt sex pheromone biosynthesis and mating in adult C. punctiferalis. Sublethal and lethal spirotetramat exposure significantly reduced pheromone production and mating success in parental (F₀) females. This correlated with dose-dependent downregulation of key pheromone pathway genes (PBANR, ACC, FAR) and suppressed ACC and trehalase enzymatic activities. Critically, sublethal effects persisted transgenerationally: F₁ offspring exhibited reduced larval/pupal weight, impaired pupation, lower adult emergence, diminished pheromone synthesis, and decreased mating success. Life-table analyses confirmed significant reductions in the intrinsic rate of increase (r) and net reproductive rate (R0) for the F₁ generation. Mechanistically, spirotetramat disrupts the PBAN/Ca²⁺/calcineurin/ACC signaling cascade and interferes with sugar metabolism, limiting essential pheromone precursors (trehalose, glucose). Thus, an ACC inhibitor designed for sucking pests effectively suppresses a chewing pest population via sublethal disruption of chemical communication and transgenerational fitness costs, highlighting its potential for adult-targeted control strategies. These findings reveal spirotetramat's potential beyond direct toxicity, highlighting its role in manipulating insect reproductive ecology. This advances understanding of pheromone dynamics and offers innovative strategies to mitigate economic impacts on agriculture.

Provided herein are novel compounds as ACC inhibitors, pharmaceutical compositions, use of such compounds in treating acne, and processes for preparing such compounds.