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

Inspired by marine natural products like kealiinines A-C, a series of 4-aryl-1<i>H</i>-naphtho[2,3-<i>d</i>]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 <b>A16</b>, <b>A17</b>, and <b>A20</b> 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). <b>A17</b> can completely control the infection of <i>Colletotrichum gloeosporioides</i> in apples at 37.5 μM over 9 days. Scanning electron microscopy (SEM) observations indicated that <b>A17</b> can damage the fungal morphology and hyphal structures. Molecular docking results showed that the 4-aryl-1<i>H</i>-naphtho[2,3-<i>d</i>]imidazole scaffold could bind well to succinate dehydrogenase (SDH). The results of seed germination tests indicated that compound <b>A17</b> 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-1<i>H</i>-naphtho[2,3-<i>d</i>]imidazole derivatives have great potential to be developed into novel fungicides.