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Deeply Optimized Nanopesticides Based on Novel Pyrimidine-Amide-Imidazole Derivatives as Dual-Target (SDH/CYP51)
Ying-Kun Yan1, Wen-Rui Chen1, Lei Hu1
1School of Science, Asymmetric Synthesis and Chirotechnology Key Laboratory of Sichuan Province, Sichuan Engineering Research Center for Molecular Targeted Diagnostic & Therapeutic Drugs, Xihua University, Chengdu 610039, P. R. China.
Abstract:
To address the increasingly severe global challenge of plant pathogenic fungal resistance, this study first synthesized a series of novel pyrimidine-amide-imidazole derivatives and loaded them onto nanomaterial carriers to construct dual-target (SDH/CYP51) antifungal nanopesticides. In vitro antifungal assays displayed that the nanopesticides 2d-MSNs and 2f-MSNs exhibited potent fungicidal activity against multiple drug-resistant fungal strains and revealed the structure-activity relationships (SARs) of the target compounds. 2d-MSNs and 2f-MSNs showed superior SDH/CYP51 inhibition (EC50 0.09-0.23 μg/mL), outperforming boscalid, prochloraz, and unmodified compounds. Furthermore, the in vivo protective and therapeutic effects illustrated that 2d-MSNs and 2f-MSNs significantly outperformed commercial fungicides. Cytotoxicity assays also confirmed the safety of 2d-MSNs and 2f-MSNs. Consequently, the nanopesticides 2d-MSNs and 2f-MSNs represent promising antifungal drug candidates.
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