关键词: 抑菌活性, 嘧啶衍生物, 分子对接, 琥铂酸脱氢酶抑制剂

Thirty-six unreported pyrimidine analogues were designed, synthesized and characterized by IR, ¹H NMR, ¹³C NMR and HRMS. Their antifungal activities were determined against five plant pathogenic fungi namely Rhizoctonia solani, Fusarum graminearum, Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea. The results indicated that most of them revealed significant antifungal activities at 20 mg/L. Among them, 4-(furan-2-yl)-2-methyl-6-(p-tolyl)pyrimidine (2c) and 4-(4-chlorophenyl)-6-(5-methylfuran-2-yl)-2-(1H-pyrazol-1-yl)pyrimidine (3d) showed the strongest activities against Sclerotinia sclerotiorum and their median effect concentrations (EC₅₀) were 0.072 and 0.077 mg/L, respectively, which implied that they had better antifungal activities than the commercial fungicide fluopyram (EC₅₀=0.244 mg/L). Meanwhile, the inhibitory activities of compounds 2c and 3d were determined against succinate dehydrogenase (SDH). The results exhibited that their half inhibitory concentrations (IC₅₀) were 0.115 and 0.121 mg/L, respectively, indicating that they also had better inhibitory activities than fluopyram (IC₅₀=0.356 mg/L). Molecular docking studies demonstrated that the binding energy of compounds 2c, 3d and fluopyram to SDH was -32.2 kJ/mol, -31.8 kJ/mol and -28.9 kJ/mol, respectively, which represented that they had stronger affinities than fluopyram. The inhibitory activities of compounds 2c and 3d against SDH have been reported for the first time.

Key words: antifungal activity, pyrimidine derivative, molecular docking, succinate dehydrogenase inhibitor