Abstract

Thirty-six novel threoninamide carbamate derivatives were designed and synthesised using active fragment-based pharmacophore model. Antifungal activities of these compounds were tested against Oomycete fungi Phytophthora capsici in vitro and in vivo. Interestingly, compound I-1, I-2, I-3, I-6 and I-7 exhibited moderate control effect (>50%) against Pseudoperonospora cubensis in greenhouse at 6.25 μg/mL, which is better than that of control. Meanwhile most of these compounds exhibited significant inhibitory against P. capsici. The other nine fungi were also tested. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum, P. piricola and R. solan in vitro with EC₅₀ values of 3.74–9.76 μg/mL. It is possible that the model is reliabile and this method can be used to discover lead compounds for the development of fungicides.

摘要

使用基于活性片段的药效团模型设计并合成了36种新型苏氨酸氨基甲酸酯氨基甲酸酯衍生物。在体外和体内测试了这些化合物对卵菌疫霉的抗真菌活性。有趣的是，化合物I-1，I-2，I-3，I-6和I-7在6.25μg/ mL的温室中表现出对立方假单胞菌孢子的中等控制作用（> 50％），优于对照。同时，这些化合物中的大多数对辣椒衣原体具有明显的抑制作用。其他九种真菌也进行了测试。更重要的是，某些化合物对菌核菌，核果假单胞菌和茄形假单胞菌在体外的EC ₅₀值为3.74–9.76μg/ mL。该模型可能是可靠的，并且该方法可用于发现用于开发杀菌剂的先导化合物。