A novel monocarbonyl curcumin analog synergizes pesticide efficiency via cytochrome P450 inhibition in the whitefly Bemisia tabaci

Synthetic insecticides remain the cornerstone of pest management in both agriculture and public health. However, their extensive application has led to the emergence of insecticide resistance, while regulatory standards are shifting toward less toxic insecticidal compounds, of natural origin (green chemicals). This study investigates the inhibitory effects of various natural products, polyphenols and synthetic curcuminoids, on cytochrome P450 CYP6CM1 from the whitefly Bemisia tabaci (BtCYP6CM1). This major agricultural pest exhibits significant insecticide resistance, which is largely mediated by the overexpression of BtCYP6CM1. Among the tested natural products, curcumin emerged as the strongest inhibitor of BtCYP6CM1 (IC50: 6.82 ± 0.54 μM). Additionally, a synthetic library of thirteen monocarbonyl curcumin analogs was screened in search of compounds with improved inhibitory potency toward BtCYP6CM1. The monocarbonyl curcumin derivative DM96 exhibited significantly enhanced inhibitory potency against BtCYP6CM1, with an IC50 value of 2.41 ± 0.24 μM. Furthermore, DM96 was evaluated as a potential synergist with imidacloprid in bioassays with adult whiteflies. The results demonstrated a substantial synergistic effect, as the combination of the curcumin derivative and imidacloprid increased B. tabaci mortality rates by up to fourfold. These findings suggest that DM96 could be a promising candidate for the development of more effective pesticide formulations, with lower toxicity and resistance breaking potential. Overall, the work contributes to the ongoing search for eco-friendly bio-pesticides and synergists that can mitigate resistance and reduce the reliance on chemical insecticides, thus supporting more sustainable agricultural practices.