Design, Synthesis, and Bioactivity of 4-Aryl-1H-naphtho[2,3-d]imidazole Derivatives as Potential Fungicides against Phytopathogenic Fungi

Inspired by marine natural products like kealiinines A–C, a series of 4-aryl-1H-naphtho[2,3-d]imidazole derivatives were designed and synthesized. The results of their antifungal activities showed that among the twenty-eight synthesized compounds, most of them showed excellent activity against nine common phytopathogenic fungi. Compounds A16, A17, and A20 exhibited remarkable antifungal potency against all fungal strains. Their average EC50 values were 28.1, 11.9, and 14.2 μM, respectively, much lower than that of azoxystrobin (EC50 = 101 μM). A17 can completely control the infection of Colletotrichum gloeosporioides in apples at 37.5 μM over 9 days. Scanning electron microscopy (SEM) observations indicated that A17 can damage the fungal morphology and hyphal structures. Molecular docking results showed that the 4-aryl-1H-naphtho[2,3-d]imidazole scaffold could bind well to succinate dehydrogenase (SDH). The results of seed germination tests indicated that compound A17 had no effect on the germination of cabbage seeds and exhibited favorable safety profiles. SAR analysis demonstrated that the introduction of an aliphatic hydrocarbon to the D ring can enhance activity against the majority of fungi. Therefore, 4-aryl-1H-naphtho[2,3-d]imidazole derivatives have great potential to be developed into novel fungicides.