Bioinsecticidal activity of actinomycete secondary metabolites against the acetylcholinesterase of the legume’s insect pest Acyrthosiphon pisum: a computational study

Abstract

Abstract Background Acyrthosiphon pisum or pea aphid is an insect of the Aphididae family, which attacks various species of legumes such as beans and peas. This pest causes economically heavy crop losses around the world. The use of conventional chemical insecticides is the only way to control its development. However, the harmful consequences of these chemicals are well known. They pollute various compartments of the environment, thus constituting a major risk for human and environmental health. The search for a more ecological alternative, respectful of the environment is, therefore, a necessity. Actinomycetes represent a source of biologically active secondary metabolites, such as antibiotics and biopesticidal agents. In this study, 150 secondary metabolites of actinomycetes have made the objective of an in silico research by molecular docking, by screening their potential inhibitors against the enzyme acetylcholinesterase (AChE) of A. pisum. Results The 3D structure of AChE, unavailable in the PDB database, was first modeled using the Modeller program, then the stereochemical quality of the model was validated. The molecular docking performed by the Autodock Vina algorithm allowed the selection of two metabolites giving binding energy equal to or lower than that of the co-crystallized inhibitor tetrahydro-acridine (−10.3Kcal/mol). The top-two metabolites are diazepinomicine (−10.9 Kcal/mol), and hygromycin (−10.3 Kcal/mol). These components have shown numerous interactions with the key residues of the catalytic site of the AChE enzyme, indicating their potential to inhibit its biological activity. The environmental and health safety of these components, as well as their bioavailability, were also studied by the verification of several pharmacokinetic and ADMET criteria. Diazepinomicine has shown excellent results verifying most of the criteria studied. A 50-ns MD simulation was also performed in order to test the stability of the complexes formed. Conclusions In addition to its favorable pharmacokinetic properties, the special chemical structure of diazepinomicin allows this molecule to interact intensely with AChE notably through the involvement of its two groups farnesyl diphosphate and dibenzodiazepinone which ensure several hydrogen and hydrophobic interactions, that offers very high stability to the complex AChE diazepinomicin. In conclusion, diazepinomicin can be suggested as a potential bioinsecticidal agent against the pest A. pisum.