Biochemical evaluation and molecular docking assessment of Cymbopogon citratus as a natural source of acetylcholine esterase (AChE)- targeting insecticides

Abstract

Acetylcholinesterase (AChE) has been an effective target for insecticide development which is a very important aspect of the global fight against insect-borne diseases. The drastic reduction in the sensitivity of insects to AChE-targeting insecticides like organophosphates and carbamates have increased the need for insecticides of natural origin. In this study, we used Drosophila melanogaster as a model to investigate the insecticidal and AChE inhibitory potentials of Cymbopogon citratus and its bioactive compounds. Flies were exposed to 100 and 200 mg/mL C. citratus leaf extract for a 3-h survival assay followed by 45 min exposure for negative geotaxis and biochemical assays. Molecular docking analysis of 45 bioactive compounds of the plant was conducted against Drosophila melanogaster AChE (DmAChE). Exposure to C. citratus significantly reduced the survival rate of flies throughout the exposure period and this was accompanied by a significant decrease in percentage negative geotaxis, AChE activity, catalase activity, total thiol level and a significant increase in glutathione-S-transferase (GST) activity. The bioactive compounds of C. citratus showed varying levels of binding affinities for the enzyme. (+)-Cymbodiacetal scored highest (-9.407 kcal/mol) followed by proximadiol (-8.253 kcal/mol), geranylacetone (-8.177 kcal/mol), and rutin (-8.148 kcal/mol). The four compounds occupied the same binding pocket and interacted with important active site amino acid residues as the co-crystallized ligand (1qon). These compounds could be responsible for the insecticidal and AChE inhibitory potentials of C. citratus and they could be further explored in the development of AChE-targeting insecticides.

Keywords: Acetylcholinesterase; Binding affinity; Cymbopogon citratus; Drosophila melanogaster.

Fig. 1

The survival rate of D. melanogaster following exposure to Cymbopogon citratus leaf extract. Values are expressed as mean ± SD (n = 5).

Fig. 2

% Negative geotaxis of D. melanogaster following exposure to Cymbopogon citratus leaf extract. Values are expressed as mean ± SD (n = 5). Values with * is significant at (p < 0.05) versus control.

Fig. 3

Acetylcholinesterase activity of D. melanogaster following exposure to 100 and 200 mg/mL of Cymbopogon citratus leaf extract. Values are expressed as mean ± SD (n = 5). Values with * is significant at (p < 0.05) versus control.

Fig. 4

Changes in catalase activity in D. melanogaster following exposure to 70% ethanolic extract of Cymbopogon citratus leaf. Values are expressed as mean ± SD (n = 5). Values with * is significant at (p < 0.05) versus control.

Fig. 5

Changes in glutathione-S-transferase activity in D. melanogaster following exposure to 70% ethanolic extract of Cymbopogon citratus leaf. Values are expressed as mean ± SD (n = 5). Values with * is significant at (p < 0.05) versus control.

Fig. 6

Changes in total thiol level in D. melanogaster following exposure to 70% ethanolic extract of Cymbopogon citratus leaf. Values are expressed as mean ± SD (n = 5). Values with * is significant at (p < 0.05) versus control.

Fig. 7

3D and 2D representations of the molecular interactions of 1qon with DmAChE.

Fig. 8

3D and 2D representations of the molecular interactions of (+)-Cymbodiacetal with DmAChE.

Fig. 9

3D and 2D representations of the molecular interactions of Proximadiol with DmAChE.

Fig. 10

3D and 2D representations of the molecular interactions of Geranylacetone with DmAChE.

Fig. 11

3D and 2D representations of the molecular interactions of Rutin with DmAChE.

Fig. 12

3D and 2D representations of the molecular interactions of (+)-Cymbodiacetal with DmAChE after Molecular Dynamics Simulation.