Synthesis and fungicidal activity of novel benzimidazole derivatives bearing pyrimidine‐thioether moiety against Botrytis cinerea

Abstract BACKGROUND Botrytis cinerea is a serious plant fungus and strongly affects the yield and quality of crops. The main control strategy is the employment of fungicides. To research for efficient fungicide with novel structure, a series of novel benzimidazole derivatives bearing pyrimidine and thioether moieties were designed and synthesized. RESULTS Some target compounds such as 4h, 4i, 4k, 4l, 4m, 4s, 4t and 4u exhibited notable fungicidal activities, with half maximal effective concentration (EC 50 ) values in the range 0.13–0.24 μg mL −1 , which means that their activities were comparable or higher than that of carbendazim (EC 50 = 0.21 μg mL −1 ). Among them, N ‐(4‐fluorophenyl)‐2‐((4‐(1 H ‐benzimidazol‐2‐yl)‐6‐(4‐methoxyphenyl) pyrimidin‐2‐yl)thio)acetamide (4m) displayed the best activity (EC 50 = 0.13 μg mL −1 ). Molecular electrostatic potential analysis of 4m elucidated that the NH moiety of benzimidazole ring was located in the positive potential region and may generate hydrogen bond with target amino acid residue. Molecular docking analysis revealed that there was one hydrogen bond and one 𝜋–𝜋 interaction between 4m and target protein. CONCLUSIONS This study demonstrated that the benzimidazole derivatives bearing pyrimidine and thioether moieties can be further optimized as a lead compound for the control of B. cinerea . The combination of molecular electrostatic potential and molecular docking analyses may provide a valuable reference for studying the interaction between the ligand and target protein. © 2021 Society of Chemical Industry.