High-Throughput Virtual Screening of Xanthene Derivatives Against a Range of Model and Real Insect Protein Structures for Developing Molecular Tools or Prototypes of New Insect Control Agents

To identify potential scaffolds for ecologically responsible pest control, six xanthene derivatives—Resuc (3-(6-hydroxy-3-oxo-3H-xanthen-9-yl)propanoic acid), Resaze (8-(6-hydroxy-3-oxo-3H-xanthen-9-yl)octanoic acid), Resac (6-hydroxy-9-methyl-3H-xanthen-3-one), Resfac (6-hydroxy-9-(trifluoromethyl)-3H-xanthen-3-one), Reshex (6-hydroxy-9-pentyl-3H-xanthen-3-one), Resaba (9-(3-aminopropyl)-6-hydroxy-3H-xanthen-3-one)—were screened using AutoDock Vina against sensory, fatty acid metabolism, reception, and transport proteins (UniProt or PDB IDs) from Leptinotarsa, Locusta, Lucilia, and Drosophila species to evaluate binding affinities (Ebind, kcal/mol).
Resfac demonstrated the highest affinity for cuticular protein A0A3Q8HFR0 (-11.4), various odorant receptors (-10.7 to -9.7), and cytochromes P450 (CYP12d1, CYP307a1, CYP4G29, CYP314a1; -10.6 to -9.6). Resac bound odorant receptors (-10.7 to -9.4; e.g., I6LU05: -10.7) and chemosensory proteins Q3LB86 (-10.7 to -10.2). Resaze displayed the highest polyspecificity, interacting with 29 targets (-10.5 to -9.0), notably cuticular protein A0A3Q8HFR0 (-10.5) and chemosensory proteins (-9.9 to -9.5). Resuc bound cuticular protein A0A3Q8HFR0 (-10.6), several odorant receptors (-10.0 to -8.8), and cytochromes P450 (e.g., CYP6a2: -9.4). Reshex interacted with cuticular protein A0A3Q8HFR0 (-9.9) and chemosensory protein Q869F2 (-9.9). Resaba bound to cuticular protein A0A3Q8HFR0 (-10.1) and odorant receptor I6LU03 (-10.3).
These profiles demonstrate the varied interaction of these xanthene scaffolds, suggesting their prospective application in the design of insect control agents or molecular probes.
Supported by BRFFR No. 20261794 and Ministry of Education grant No. 20261474.