Design, Synthesis,\nand Assessment of Fungicidal Activity\nof Active Substructure 1,2,4-Triazole Containing Coumarin

Fragment splicing and molecular docking are important\ntechniques\nin the design of new agrochemicals. Based on our former discovery\nof 4-(3,4-dichloroisothiazole)-7-hydroxycumarins <b>1a</b> and <b>1b</b> as fungicidal leads, following fragment splicing and molecular\ndocking, a series of bioactive substructure 1,2,4-triazole containing\ncoumarins were designed and synthesized. In vitro fungicidal bioassay\nindicated that compound <b>7e</b> was more active than <b>1b</b> against Botrytis cinereal, Cercospora arachidicola, and Sclerotinia sclerotiorum, with a corresponding EC<sub>50</sub> value of 4.02 vs 5.90, 6.03 vs 8.31, and 3.81 vs 5.37 μg/mL,\nrespectively. Compound <b>7e</b> also showed an EC<sub>50</sub> value of 4.15 μg/mL against Fusarium graminearum. Moreover, compound <b>7e</b> demonstrated a stronger inhibition\nthan flutriafol against F. graminearum 14-α demethylase, with an IC<sub>50</sub> value of 0.59 and\n0.97 μM, respectively. Calculation results based on density\nfunctional theory calculation (DFT), molecular dynamics (MD), and\nmolecular mechanics/Poisson–Boltzmann surface area (MM/PBSA)\nstudies gave a rational explanation between the activity of compound <b>7e</b> and its structure. This study demonstrates that fragment\nsplicing of 1,2,4-triazole and coumarin is a good technique for discovering\na novel fungicide lead.