Citation: Yan Yingkun, Cheng Wei, Xiao Tingting, Zhang Guilan, Zhang Tingting, Lu Tong, Tang Xiaorong. Discovery of Novel 2, 4, 6-Trisubstituted Pyrimidine Derivatives as Succinate Dehydrogenase Inhibitors[J]. Chinese Journal of Organic Chemistry, ;2020, 40(12): 4237-4248. doi: 10.6023/cjoc202005057 shu

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

School of Science, Xihua University, Chengdu 610039

Corresponding author: Tang Xiaorong, tangxr112@126.com

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Received Date: 21 May 2020
Revised Date: 30 June 2020
Available Online: 11 August 2020
Fund Project: 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)the Chunhui Programs of the Ministry of Education 191653the Undergraduate Innovation and Entrepreneurship Training Programs of Xihua University 201810623009the Technical Innovation Programs of Chengdu Municipal Bureau of Science and Technology 2018-YF05-00970-SNthe Innovation Fund of Postgraduate of Xihua University YCJJ2019025

Figures(6)

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.
- antifungal activity,
- pyrimidine derivative,
- molecular docking,
- succinate dehydrogenase inhibitor
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