Design, Synthesis, and Bioactivity of Spiro Derivatives Containing a Pyridine Moiety

• Published in: Journal of agricultural and food chemistry Vol. 70; no. 50; pp. 15726 - 15736
• Main Authors: Yu, Lijiao, Guo, Shengxin, Wang, Ya, Liao, Anjing, Zhang, Wei, Sun, Ping, Wu, Jian
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.12.2022; Amer Chemical Soc
• Subjects: Agricultural and Environmental Chemistry; Agriculture; Agriculture, Multidisciplinary; Antiviral Agents - chemistry; Chemistry; Chemistry, Applied; Drug Design; Food Science & Technology; Life Sciences & Biomedicine; Molecular Docking Simulation; Physical Sciences; Pyridines - chemistry; Pyridines - pharmacology; Science & Technology; Structure-Activity Relationship; Tobacco Mosaic Virus; synthesis; structure−activity relationships; antiviral activities; pyridine spiro; insecticidal activities; preliminary mechanism; CHAIN; TOBACCO-MOSAIC-VIRUS; COAT PROTEIN; structure-activity relationships; ANTIVIRAL ACTIVITY; AGENTS; DISCOVERY
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.2c06189

We designed and synthesized a series of pyridine spiro derivatives and evaluated their insecticidal and antiviral activities. Some compounds exhibited good insecticidal and antiviral activities. Notably, the E series of compounds displayed good insecticidal activity against Tetranychus urticae. Compounds E20 (EC50 = 63.68 mg/L) and F4 (EC50 = 47.81 mg/L) exhibited inactivation activities against the tobacco mosaic virus (TMV), which were similar to that of Ningnanmycin (EC50 = 58.01 mg/L). Molecular docking showed that compounds E20 and F4 exhibited satisfactory affinities for the TMV coat protein (TMV-CP), with binding energies (−6.7 and −6.4 kcal/mol, respectively) slightly lower than that of Ningnanmycin (−6.3 kcal/mol). Further, molecular dynamics analysis revealed that compounds E20 and F4 exhibited better binding stability values than Ningnanmycin. Microscale thermophoresis showed that compounds E20 (K d = 0.053 ± 0.016 μM) and F4 (K d = 0.045 ± 0.022 μM) bound more strongly to TMV-CP than Ningnanmycin (K d = 0.10 ± 0.029 μM). The results of transmission electron microscopy showed that these two compounds hindered the self-assembly and growth of TMV. In summary, we showed that these pyridine spiro derivatives could be used as a basis for the research and development of novel pesticides.