Design, Synthesis, and Assessment of Fungicidal Activity of Active Substructure 1,2,4-Triazole Containing Coumarin.

Fragment splicing and molecular docking are important techniques in the design of new agrochemicals. Based on our former discovery of 4-(3,4-dichloroisothiazole)-7-hydroxycumarins and as fungicidal leads, following fragment splicing and molecular docking, a series of bioactive substructure 1,2,4-triazole containing coumarins were designed and synthesized. In vitro fungicidal bioassay indicated that compound was more active than against , , and , with a corresponding EC value of 4.02 vs 5.90, 6.03 vs 8.31, and 3.81 vs 5.37 μg/mL, respectively. Compound also showed an EC value of 4.15 μg/mL against . Moreover, compound demonstrated a stronger inhibition than flutriafol against 14-α demethylase, with an IC value of 0.59 and 0.97 μM, respectively. Calculation results based on density functional theory calculation (DFT), molecular dynamics (MD), and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) studies gave a rational explanation between the activity of compound and its structure. This study demonstrates that fragment splicing of 1,2,4-triazole and coumarin is a good technique for discovering a novel fungicide lead.