AMIDE DERIVATIVES OF 1,2,4-OXADIAZOLE AS PROMISING AGENTS WITH DUAL FUNGICIDAL AND NEMATICIDAL ACTIVITY
DOI:
https://doi.org/10.32782/pcsd-2025-4-9Keywords:
1,2,4-oxadiazole, amide derivatives, synthesis, fungicidal activity, nematicidal activity, succinate dehydrogenase (SDH), structure-activity relationships (SAR)Abstract
Fungal and nematode pathogens, which often act synergistically, pose a significant threat to food security. Conventional plant protection methods involve the use of separate fungicides or nematicides, which increases chemical load and promotes the development of resistance. A promising approach is the design of dual-action molecules that can simultaneously suppress both fungal and nematode pathogens. Particular attention is drawn to amide derivatives of 1,2,4-oxadiazole due to their chemical modularity, heteroatomic composition, and favourable toxicity profile. These compounds exhibit a high level of succinate dehydrogenase (SDH) inhibition, leading to the blockade of electron transport, disruption of oxidative phosphorylation, and energy depletion in pathogens. This study employed a systematic review of publications in Scopus, Web of Science, and PubMed. A comparative analysis of synthetic strategies for amide 1,2,4-oxadiazoles was conducted, and data on their fungicidal and nematicidal activities were systematised using structure-activity relationship (SAR) analysis to identify key structural-activity patterns. The analysis demonstrated that maximal activity is achieved through the combination of heteroaromatic substituents (notably pyridyl groups), optimal halogenation, and a flexible amide linker, which ensures proper orientation of the molecule within the enzyme’s active site. Key structural fragments responsible for high biological efficacy were identified, and recommendations for optimizing synthetic protocols were proposed. Further optimization can be achieved through modular molecular design, balancing hydrophobicity, and integrating secondary mechanisms of action, including reactive oxygen species generation, while minimizing toxicity and the risk of bioaccumulation (ecological SAR). The introduction of amide 1,2,4-oxadiazole derivatives as innovative dual-action agents presents prospects for enhancing crop productivity, reducing the frequency of applications, and mitigating the development of resistance.
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