Design, Synthesis, and Antifungal Activities of 3-Acyl Thiotetronic Acid Derivatives: New Fatty Acid Synthase Inhibitors
Design, Synthesis, and Antifungal Activities of 3-Acyl Thiotetronic Acid Derivatives: New Fatty Acid Synthase Inhibitors
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DOI：
10.1021/acs.jafc.7b05491
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发表时间：
2018-01-31
影响因子：
6.1
通讯作者：
Hua, Rimao
中科院分区：
文献类型：
--
作者：
Lv, Pei;Chen, Yiliang;Hua, Rimao
新出现的真菌性植物病日益成为粮食安全威胁。设计、合成、表征了26个新的3-酰基硫代特窗酸衍生物，并对其进行了抗苹果腐烂病、新月弯孢菌、禾谷镰刀菌和尖孢镰刀菌活性评价。番茄叶锈菌在26个化合物中，6 f对苹果枯萎病菌、苹果炭疽病菌lunata、新月弯孢F. graminearum和F. oxysporum F.对番茄晚疫病菌的半数有效浓度（EC_（50））分别为4.1、3.1、3.6和4.1 μ g/mL，而杀菌剂嘧菌酯的相应EC_（50）分别为0.14、6.7、22.4和4.3 μ g/mL，杀菌剂多菌灵的相应EC_（50）分别为4.2、41.7、0.42和0.12 μ g/mL;和>50、0.19、0.43和BS > 50 μ g/mL的杀真菌剂氟吡菌酰胺。对苹果枯萎病菌脂肪酸合成酶的抑制作用与体外抗真菌活性一致。分子对接表明3-酰基硫代特窗酸衍生物靶向C171 QKasA复合物。这些发现有助于理解新型强效杀菌剂的作用模式和设计与合成。
Emerging fungal phytodiseases are increasingly becoming a food security threat. Twenty-six new 3-acylthiotetronic acid derivatives were designed, synthesized, characterized, and evaluated for activities against Valsa mali, Curvularia lunata, Fusarium graminearum, and Fusarium oxysporum f. sp. lycopersici. Among the 26 compounds, 6f was the most effective against V. mali, C. lunata, F. graminearum, and F. oxysporum f. sp. lycopersici with median effective concentrations (EC50) of 4.1, 3.1, 3.6, and 4.1 mu g/mL, respectively, while the corresponding EC50 were 0.14, 6.7, 22.4, and 4.3 mu g/mL of the fungicide azoxystrobin; 4.2, 41.7, 0.42, and 0.12 mu g/mL of the fungicide carbendazim; and >50, 0.19, 0.43, and BS > 50 mu g/mL of the fungicide fluopyram. The inhibitory potency against V. mali fatty acid synthase agreed well with the in vitro antifungal activity. The molecular docking suggested that the 3-acylthiotetronic acid derivatives targeted the C171QKasA complex. The findings help understanding the mode of action and design and synthesis of novel potent fungicides.