Coumarin-1,2,4-Triazole hybrids as potential agents against Brassicogethes aeneus (Fabricius 1775).

The development of new highly effective active substances for environmentally safer insecticides is increasingly required due to the development of resistance to commonly used pesticides and restrictions on insecticide use within the European Union. The insecticidal potential of coumarin-1,2,4-triazole hybrids (CTHs) was evaluated against pollen beetle Brassicogethes aeneus (Fabricius 1775) and honey bees (Apis mellifera). The highest insecticidal activity against B. aeneus within the first 24 h was observed for the CTH N-4 unsubstituted derivative 2o (100%), and for compounds bearing hydrophobic substituents at the same position, including benzyl (2c, 100%), fluorophenyl (2g, 84.21%), and p-tolyl group (2j, 78.95%) at the same position. Acute oral toxicity predictions using the BeeToxAI web application classified all CTHs as non-toxic, and experimental validation confirmed the absence of acute oral toxicity in A. mellifera for ten selected compounds within the standard 96 h assessment window. A quantitative structure-activity relationship (QSAR) study generated a predictive multiple linear regression model (R2 = 0.787; F = 23.372; CCCtr = 0.881; CCCcv = 0.815; R2ext = 0.719; CCCext = 0.847) based on WHIM, Moran autocorrelation and information molecular descriptors. The QSAR model indicated that molecular features associated with lipophilicity at the triazole N-4 position contribute to enhanced insecticidal activity.