Synthesis, Antifungal Evaluation, and Quantitative Structure-Activity Relationship of Camptothecin Derivatives...

Plant pathogenic fungi cause major crop losses, demanding new fungicides with novel chemotypes. Here, we designed and synthesized camptothecin (CPT) derivatives through systematic A-, B-, and E-ring modifications and evaluated their in vitro activities against six phytopathogenic fungi. Most derivatives showed enhanced broad-spectrum inhibition. Notably, compound B5 showed exceptional efficacy, with EC₅₀ values ranging from 4.73 ng/mL to 0.102 μg/mL against these pathogens. Furthermore, in vivo assays demonstrated that B5 exhibited superior curative and protective activity against Magnaporthe oryzae infections in rice leaves compared to the commercial fungicides Carbendazim and Boscalid. Preliminary mechanistic studies demonstrated that B5 exerts its antifungal effects through the inhibition of spore germination, disruption of hyphal morphology, impairment of cell wall and membrane integrity, and induction of reactive oxygen species accumulation. QSAR analysis further identified key mass/electronic descriptors governing activity, providing guidance for the rational optimization of CPT-based fungicides.