A novel bee‐friendly peptidomimetic insecticide: Synthesis, aphicidal activity and 3D‐QSAR study of insect kinin analogs at Phe² modification

Abstract

BACKGROUND: As one of the most abundant and destructive pests in agriculture, aphids cause significant damage to crops due to their sap-taking and as virus vectors. Chemical insecticides are the most effective method to control aphids, but they bring insecticide resistance problems and harm nontarget organisms, especially bees, therefore the search for novel eco-friendly aphid control agents with low bee toxicity is urgent. Insect kinins are a class of small neuropeptides that control important functions in insects. In our previous study, we found insect kinin analog IV-3 has good aphicidal activity and the location of the aromatic ring on the side chain of Phe 2 is the key to the formation of the ⊎-turn resulting in the biological activity of insect kinin analogs. However, there are few studies on insect kinin Phe 2 substitution and modification, and its structure-activity relationship is still unclear.RESULTS: In this project, 44 insect kinin analogs with the Phe 2 modification, replacing it with different natural or unnatural amino acids, were designed and synthesized based on the lead IV-3 to explore the role of the Phe 2 residues. Bioassays with soybean aphids of Aphis glycines indicated that nine analogs have better aphicidal activity than the lead IV-3. In particular, compound L 25 exhibits excellent aphicidal activity (LC 50 = 0.0047 mmol L −1 ) and has low toxicity to bees. Furthermore, a reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) was established to produce a helpful clue that introducing hydrophobic groups away from the backbone chain is beneficial to improve aphicidal activity.CONCLUSION: The residue Phe 2 of insect kinin analogs is the key position and has a significant impact on the activity. L 25 has a high toxicity for aphids, while a low toxicity to bees, and therefore can be considered as a lead compound to develop new biosafe aphid control agents. Finally, we provide a useful 3D-QSAR model as theoretical guidance for further structural optimization.

Aphid‐repellent, ladybug‐attraction activities, and binding mechanism of methyl salicylate derivatives containing geraniol moiety

“…The test was carried out according to the reported method. 50 Sucrose water and the solvent were used as the blank control and negative control, respectively. Each experiment was performed in three replicates and each replicate contained ten bees.…”

Natural Product-Based Crop Protection Compounds─Origins and Future Prospects

“…The recent development and commercialization of a spider venom-based GS-omega/kappa Hxtx Hv1a peptide for pest insect control highlights the viability of this approach. Importantly, this peptide-insecticide also brings to light a new insecticidal MoA. , Similarly, recent studies suggest that some insect neuropeptides may have potential as models for synthetic peptide insecticides, with some displaying efficacy in the laboratory bioassays comparable to commercial insecticides . It may also be possible to devise small-molecule synthetic mimics of some insect neuropeptides, providing another avenue to exploiting these types of molecules with their new MoAs.…”

Green Design, Synthesis, and Molecular Docking Study of Novel Quinoxaline Derivatives with Insecticidal Potential against Aphis craccivora

“… 25 Unfortunately, there are many limitations of kinins for application in peptidase inactivation and easy degradation. 26 …”

“…Insect kinins exhibited aphicidal and antifeedant potential that can control and interfere with biological processes of insects such as muscle contraction, release of digestive enzymes, and water–sodium balance that lead to insect death . Unfortunately, there are many limitations of kinins for application in peptidase inactivation and easy degradation …”

“…25 Unfortunately, there are many limitations of kinins for application in peptidase inactivation and easy degradation. 26 Quinoxaline-based compounds are among some molecular structures that have been recorded to be used for many different purposes in agrochemistry and medicine because of their biological potential as anti-inflammatory, 27−29 bial, 30−32 antifungal, 33,34 antibiotic, 35,36 and insecticidal agents. 37−39 Moreover, quinoxalines were reported in the literature to be active inhibitors of nicotinic acetylcholine.…”