Molecular docking analysis of andrograpanin interactions with acetylcholinesterase from Aedes aegypti and Culex quinquefasciatus

Vector-borne diseases pose a significant and ongoing threat to global public health. The increasing resistance of insect vectors to conventional chemical insecticides highlights the need for alternative control measures. Plant-derived compounds, known for their bioactive properties, present promising candidates in this context. This study is the first to investigate the potential molecular interactions between andrograpanin and acetylcholinesterase (AChE1) from Aedes aegypti and Culex quinquefasciatus using molecular docking. AChE, a key enzyme in neurotransmission, is a target for insecticidal agents due to its role in breaking down acetylcholine in the central nervous system. Ligand structures of andrograpanin and the standard insecticide temephos were prepared using Chem Draw Ultra, and AChE1 models for Ae. aegypti and Cx. quinquefasciatus were generated through homology modeling with SWISS-MODEL, using an Anopheles gambiae AChE mutant as a template. Molecular docking analysis was performed using AutoDock Tools, where binding energies and ligand efficiencies were calculated. Andrograpanin displayed moderately favourable predicted binding affinities and interaction profiles with AChE1 from both mosquito species compared to temephos, suggesting that AChE1 may represent a potential molecular target and generating a mechanistic hypothesis for the observed mosquitocidal activity. Notably, andrograpanin formed stable hydrogen and hydrophobic interactions, with binding energies of -6.36 kcal/mol and − 6.45 kcal/mol for Ae. aegypti and Cx. quinquefasciatus , respectively, surpassing temephos. These findings indicate that andrograpanin exhibits moderately favourable predicted binding interactions with AChE1 and may serve as a promising lead compound for future development of eco-friendly insecticidal agents. However, the proposed mechanism of AChE1 inhibition remains a computational hypothesis based on molecular docking and has not yet been verified through direct acetylcholinesterase inhibition assays.