In-silico Assessment of the effects of Hyptis suaveolens as a natural source of Acetylcholine esterase (AchE )- targeting insecticide

Developing effective insecticides is crucial to the global fight against vector-borne diseases, epidemics, and pandemics. Acetylcholinesterase (AChE), a serine hydrolase responsible for regulating acetylcholine levels in various organisms, is one of the most common targets of synthetic insecticides such as organophosphates and carbamates. However, widespread exposure to these chemicals has led to a significant decline in insect sensitivity, necessitating higher effective doses and consequently increasing human exposure to their toxic effects. As a result, the search for safer and more effective insecticides derived from natural sources has gained significant attention. This study aimed to computationally evaluate the AChE inhibitory potential of bioactive compounds from Hyptis suaveolens (L.) Poit, a medicinal plant widely used in traditional medicine across tropical regions. Using in silico approaches, 39 bioactive compounds were assessed through molecular docking, ligand and protein preparation, and toxicity prediction, utilizing computational tools such as Lotus, Chimera, PyRx, and ProTox3. Docking analysis revealed that Hyptis suaveolens compounds exhibited binding affinities ranging from − 10.5 to -3.8 kcal/mol against AChE. The standard reference ligand, 9-(3-phenylmethylamino)-1,2,3,4-tetrahydroacridine (C₂₀H₂₀N₂), had a docking score of -9.3 kcal/mol. Among the tested compounds, LTS0222826 exhibited the strongest binding affinity (-10.5 kcal/mol), followed by LTS0163613 (-9.7 kcal/mol), while LTS0238624 showed the weakest binding affinity (-3.8 kcal/mol). Additionally, LTS0163613 and LTS0107905 exhibited the least predicted toxicological effects on human physiological systems. Notably, both compounds showed no adverse effect on the respiratory system and other key biological functions when administered orally. This suggests their potential safety as natural insecticides and insect repellents, supporting their further exploration as alternatives to synthetic chemical insecticides.