Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (12): 4237-4248.DOI: 10.6023/cjoc202005057 Previous Articles     Next Articles


严映坤, 程玮, 肖婷婷, 张桂兰, 张婷婷, 陆童, 唐孝荣   

  1. 西华大学理学院 成都 610039
  • 收稿日期:2020-05-21 修回日期:2020-06-30 发布日期:2020-08-11
  • 通讯作者: 唐孝荣
  • 基金资助:

Discovery of Novel 2,4,6-Trisubstituted Pyrimidine Derivatives as Succinate Dehydrogenase Inhibitors

Yan Yingkun, Cheng Wei, Xiao Tingting, Zhang Guilan, Zhang Tingting, Lu Tong, Tang Xiaorong   

  1. School of Science, Xihua University, Chengdu 610039
  • Received:2020-05-21 Revised:2020-06-30 Published:2020-08-11
  • Supported by:
    Project supported by the Chunhui Programs of the Ministry of Education (No. 191653), the Technical Innovation Programs of Chengdu Municipal Bureau of Science and Technology (No. 2018-YF05-00970-SN), the Innovation Fund of Postgraduate of Xihua University (No. YCJJ2019025) and the Undergraduate Innovation and Entrepreneurship Training Programs of Xihua University (No. 201810623009).

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