SAR and QSAR Studies of Citral‐Based Derivatives Against Colletotrichum fructicola

To develop citral‐based botanical fungicides, 112 previously reported derivatives across 5 series were evaluated in vitro against Colletotrichum fructicola . SAR analysis identified the citral‐thiourea series as the most potent group, with 3‐methoxy derivative c18 showing the highest intraseries activity. Notably, intermediates d (EC 50 = 0.7474 mg/L, EC 90 = 6.0319 mg/L) and g (EC 50 = 0.1073 mg/L, EC 90 = 0.6244 mg/L) demonstrated exceptional efficacy, significantly outperforming commercial chlorothalonil (EC 50 = 1.4382 mg/L, EC 90 = 268.5969 mg/L), with intermediate g emerging as the most potent compound overall. A predictive QSAR model was successfully constructed ( R 2 = 0.8345), revealing that lower polarity, enhanced electronic stability of carbon–hydrogen bonds, higher localized solvation energy, and minimized steric hindrance favor antifungal potency. Furthermore, MTT assays confirmed that derivative g exhibits low cytotoxicity toward human liver and kidney cells, substantially lower than raw citral. This work provides a solid theoretical framework for designing highly active inhibit C. fructicola agents. A library of 112 previously reported citral derivatives is screened to identify potent botanical fungicides against Colletotrichum fructicola . A predictive QSAR model ( R 2 = 0.8345) decrypts structural pathways, elegantly balancing global transmembrane transport with localized target anchoring. Providing exceptional efficacy and low cytotoxicity, these insights offer a definitive blueprint for the next‐generation green pesticides.