Larvicidal activity and molecular interactions of furoquinoline alkaloids from Araliopsis soyauxii with wild-type and G119S mutant acetylcholinesterase of the malaria vector Anopheles gambiae

Abstract The use of synthetic insecticides has led to target-site mutations such as G119S in acetylcholinesterase which is a major threat in Anopheles gambiae mosquitoes’ control. To obtain alternative sources of novel bio-friendly insecticides, our study investigated the larvicidal activity and molecular interactions of four alkaloids isolated from Araliopsis soyauxii (Rutaceae) Nkolbisine, Tecleaverdoornine, Kokusaginine, and Flindersiamine against insecticide-susceptible and resistant An. gambiae populations. The alkaloids of the A. soyauxii were obtained from stem barks using column chromatography and characterized by NMR spectroscopy. Using WHO larvicidal bioassays protocol, the susceptible Kisumu strain and field collected strains of An. gambiae populations characterized as carrying G119S Ace-1 mutation were exposed to the purified alkaloids. Molecular interactions analysis was conducted via Molecular docking and MM-GBSA analysis. Nkolbisine was the most potent, with LC 50 values ranging from 51.63 mg/L to 60.12 mg/L across various strains at 24 h. Tecleaverdoornine was also very active and Kokusaginine and Flindersiamine followed. Our docking results revealed that Nkolbisine and Tecleaverdoornine had a positive binding affinity to wild-type as well as mutant AChE, with docking of scores − 8.94 and − 7.75 kcal/mol (wild-type) and − 9.25 and − 7.90 kcal/mol (mutant), respectively. Interactions such as hydrogen bonding with catalytic residues (GLU448, SER283) and π-π stacking were conserved in aromatic residues (TYR493, TRP441). MM-GBSA analysis, showed that Nkolbisine (-46.27 to -29.39 kcal/mol) interacts favorably with both enzymes. Hence, Nkolbisine and Tecleaverdoornine are eco-friendly potential larvicidal candidates that can be used against both susceptible and resistant populations of An. gambiae for larval control in endemic settings.