Virtual screening and in vitro activity of potential insecticidal agents from natural products

Insecticides research must explore alternative pathways to identify small compounds that satisfy the needs of farmers in both developing and developed countries. Reducing the cost of these inputs is essential to increasing agricultural production and mitigating food insecurity. In this study, a multi-stage computational screening of 407615 natural products were conducted, utilizing filters for volatility (MW < 350Da), Protein-Ligand Interaction Fingerprint (PLIF) similarity to a tacrine reference, and a commercial cost threshold of less than 8USD/g. Out of 16 finalists evaluated in vitro, two compounds demonstrated significant inhibitory activity against Acetylcholinesterase from Electrophorus electricus (52% and 77% at 250μM, respectively) and Drosophila melanogaster. Kinetic analysis of one novel compound, the most potent lead (K_i=88.1±3.1μM), revealed a mixed-type inhibition mechanism. These results validate the identification of affordable, reversible, and volatile natural scaffolds that serve as promising optimizable fragments for the development of sustainable biopesticides.