Antifungal Exploration of Quinoline Derivatives against Phytopathogenic Fungi Inspired by Quinine Alkaloids
Antifungal Exploration of Quinoline Derivatives against Phytopathogenic Fungi Inspired by Quinine Alkaloids
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受奎宁生物碱启发的喹啉衍生物对植物病原真菌的抗真菌探索
DOI：
10.1021/acs.jafc.1c05677
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发表时间：
2021-10-08
影响因子：
6.1
通讯作者：
Tang, Chen
中科院分区：
文献类型：
--
作者：
Chen, Yong-Jia;Ma, Kun-Yuan;Tang, Chen
受前期奎宁结构简化和天然产物抗植物病原真菌创新应用研究的启发，本论文选择先导结构2，8-二（三氟甲基）-4-羟基喹啉（3）作为候选化合物，对其进行了多样化的设计、合成和抗真菌活性评价。对所合成的化合物Aa 1-Db 1进行了抗灰葡萄孢、禾谷镰刀菌、立枯丝核菌和核盘菌的活性评价。结果表明，化合物Ac 3，Ac 4，Ac 7，Ac 9，Ac 12，Bb 1，Bb10，Bb 11，Bb 13，Cb 1. Cb 3对S. sclerotiorum和B.灰霉病菌（cinerea）的活性，分别比先导化合物3（1.72和1.89 μ g/mL）、市售杀菌剂嘧菌酯（azoxystrobin）（均>30 μ g/mL）和8-羟基喹啉（2.12和5.28 μ g/mL）的活性强。此外，化合物Ac 12显示出优异的体内抗真菌活性，其活性与商业杀菌剂啶酰菌胺相当。初步机制表明，化合物Ac 12可能导致细胞膜形态异常，膜通透性增加，细胞内容物释放。这些结果表明，Ac 12具有较上级的体内外杀菌活性，有望成为一种潜在的植物病原真菌的拮抗剂。
Enlightened from our previous work of structural simplification of quinine and innovative application of natural products against phytopathogenic fungi, lead structure 2,8-bis(trifluoromethyl)-4-quinolinol (3) was selected to be a candidate and its diversified design, synthesis, and antifungal evaluation were carried out. All of the synthesized compounds Aa1-Db1 were evaluated for their antifungal activity against four agriculturally important fungi, Botrytis cinerea, Fusarium graminearum, Rhizoctonia solani, and Sclerotinia sclerotiorum. Results showed that compounds Ac3, Ac4, Ac7, Ac9, Ac12, Bb1, Bb10, Bb11, Bb13, Cb1. and Cb3 exhibited a good antifungal effect, especially Ac12 had the most potent activity with EC50 values of 0.52 and 0.50 mu g/mL against S. sclerotiorum and B. cinerea, respectively, which were more potent than those of the lead compound 3 (1.72 and 1.89 mu g/mL) and commercial fungicides azoxystrobin (both >30 mu g/mL) and 8-hydroxyquinoline (2.12 and 5.28 mu g/mL). Moreover, compound Ac12 displayed excellent in vivo antifungal activity, which was comparable in activity to the commercial fungicide boscalid. The preliminary mechanism revealed that compound Ac12 might cause an abnormal morphology of cell membranes, an increase in membrane permeability, and release of cellular contents. These results indicated that compound Ac12 displayed superior in vitro and in vivo fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.