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 (EC₅₀ = 0.7474 mg/L, EC₉₀ = 6.0319 mg/L) and g (EC₅₀ = 0.1073 mg/L, EC₉₀ = 0.6244 mg/L) demonstrated exceptional efficacy, significantly outperforming commercial chlorothalonil (EC₅₀ = 1.4382 mg/L, EC₉₀ = 268.5969 mg/L), with intermediate g emerging as the most potent compound overall. A predictive QSAR model was successfully constructed (R² = 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.