Discovery of evodiamine derivatives as potent insecticide candidates

Liu, Jingbo; Shi, Yabing; Chen, Shuting; Li, Fengyun; Wen, Wen

doi:10.1016/j.bmc.2022.116727

Cited by 3 publications

(4 citation statements)

References 26 publications

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“…Based on the aforementioned findings and our prior work, , to explore the influence of R 1 substituents in the A ring on larvicidal activity, we synthesized compounds 21a–f . The results in Table showcased that compounds 21a–f exhibited markedly improved larvicidal activity compared to the parent evodiamine, reinforcing the results that verified that the introduction of the cyclopropyl sulfonyl group at the nitrogen atom of the B ring could improve larvicidal activity significantly.…”

Section: Results and Discussionmentioning

confidence: 99%

“…This observation highlighted the significant role played by the fluorine atom in the E ring in augmenting larvicidal activity, in line with our prior research. 31,32 Subsequently, we designed and synthesized compounds 21m (R 2 = 1-F), 21n (R 2 = 3-F), and 21o (R 2 = 4-F) and found that 21m exhibited much better larvicidal activity than that of 21i, 21n, and 21o, indicating that the fluorine atom at position 1 of the E ring could enhance larvicidal activity.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…Molecular Docking. Drawing upon our previous research 31,32 and the results of the calcium imaging experiments, we proceeded to validate whether the evodiamine-based sulfonamide derivatives targeted insect RyRs. To achieve this, we docked 21m and CHL into normal P. xylostella RyRs, which was constructed using homology modeling.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…29,30 Our prior studies have established that evodiamine and its derivatives target insect ryanodine receptors (RyRs), akin to chlorantraniliprole (CHL), and that some derivatives exhibit robust larvicidal activity against oriental armyworm Mythimna separata (M. separata) and diamondback moth P. xylostella (P. xylostella) (Figure 1). 31,32 Taking all of these facets into account, our efforts aimed to further explore the potential of the evodiamine scaffold as a basis for novel insecticides. A series of novel evodiamine-based derivatives were designed and synthesized (Figure 1), and their larvicidal activity against the third instar larvae of M. separata and P. xylostella was assessed.…”

Section: ■ Introductionmentioning

confidence: 99%

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Novel Evodiamine-Based Sulfonamide Derivatives as Potent Insecticide Candidates Targeting Insect Ryanodine Receptors

Liu,

Guo,

Zhong

et al. 2024

J. Agric. Food Chem.

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Pests represent an important impediment to efficient agricultural production and pose a threat to global food security. On the basis of our prior research focused on identifying insecticidal leads targeting insect ryanodine receptors (RyRs), we aimed to identify evodiamine scaffold-based novel insecticides. Thus, a variety of evodiamine-based derivatives were designed, synthesized, and assessed for their insecticidal activity against the larvae of Mythimna separata (M. separata) and Plutella xylostella (P. xylostella). The preliminary bioassay results revealed that more than half of the target compounds exhibited superior activity compared to evodiamine, matrine, and rotenone against M. separata. Among these, compound 21m displayed the most potent larvicidal efficiency, with a remarkable mortality rate of 93.3% at 2.5 mg/L, a substantial improvement over evodiamine (10.0% at 10 mg/L), matrine (10.0% at 200 mg/L), and rotenone (30.0% at 200 mg/L). In the case of P. xylostella, compounds 21m and 21o displayed heightened larvicidal activity, boasting LC50 values of 9.37 × 10–2 and 0.13 mg/L, respectively, surpassing that of evodiamine (13.41 mg/L), matrine (291.78 mg/L), and rotenone (18.39 mg/L). A structure–activity relationship analysis unveiled that evodiamine-based derivatives featuring a cyclopropyl sulfonyl group at the nitrogen atom of the B ring and a fluorine atom in the E ring exhibited more potent larvicidal effects. This finding was substantiated by calcium imaging experiments and molecular docking, which suggested that 21m could target insect RyRs, including resistant mutant RyRs of P. xylostella (G4946E and I4790M), with higher affinity than chlorantraniliprole (CHL). Additionally, cytotoxicity assays highlighted that the potent compounds 21i, 21m, and 21o displayed favorable selectivity and low toxicity toward nontarget organisms. Consequently, compound 21m emerges as a promising candidate for further development as an insecticide targeting insect RyRs.

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Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%