In silico molecular docking analysis on acetylcholinesterase (AChE) inhibition activity on Aedes aegypti and Culex quinquefasciatus by β-isocostic acid

Abstract

The increasing prevalence of mosquito-borne diseases poses serious public health and economic threats, further exacerbated by the emergence of insecticide resistance in mosquito populations. Although conventional insecticides are effective, they contribute to environmental degradation and resistance development. This study investigates the insecticidal potential of β-isocostic acid, a plant-derived compound that targets acetylcholinesterase (AChE) to disrupt neurotransmission in Aedes aegypti and Culex quinquefasciatus, two major mosquito vectors. Molecular docking was employed to evaluate and compare the AChE binding affinity and interaction patterns of β-isocostic acid with that of the standard insecticide temephos. Ligand structures were retrieved from PubChem and optimized using ChemDraw and the PRODRG server. Homology models of AChE1 for Ae. aegypti and Cx. quinquefasciatus were constructed based on the crystal structure of an Anopheles gambiae AChE mutant. Docking simulations were performed using AutoDock Tools with a grid-based approach and the Lamarckian Genetic Algorithm. β-Isocostic acid demonstrated strong binding affinity to AChE1 in both species, with binding energies of –8.2 kcal/mol for Ae. aegypti and –8.5 kcal/mol for Cx. quinquefasciatus, values comparable to those of temephos (–8.7 kcal/mol and –9.1 kcal/mol, respectively). These findings suggest that β-isocostic acid may serve as an eco-friendly insecticidal candidate, inhibiting AChE and impairing mosquito function. Given its promising binding profile, β-isocostic acid has potential as a sustainable alternative for mosquito control. Further in vivo studies are warranted to validate its efficacy and safety.