Novel carboxylated pyrroline-2-one derivatives bearing a phenylhydrazine moiety: Design, synthesis, antifungal evaluation and 3D-QSAR analysis
Novel carboxylated pyrroline-2-one derivatives bearing a phenylhydrazine moiety: Design, synthesis, antifungal evaluation and 3D-QSAR analysis
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带有苯肼部分的新型羧化吡咯啉-2-酮衍生物：设计、合成、抗真菌评估和 3D-QSAR 分析
DOI：
10.1016/j.bmcl.2020.127519
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发表时间：
2020-11-01
影响因子：
2.7
通讯作者：
Yang, Chunlong
中科院分区：
文献类型：
--
作者：
Chen, Min;Zhang, Lizhi;Yang, Chunlong
为了发现具有创新作用机制的新型高效抗真菌先导化合物，本文首次设计并合成了23个含苯肼基的羧基吡咯啉-2-酮衍生物。体外生物活性测定结果表明，大部分化合物对禾谷镰刀菌（Fg）、番茄灰霉病菌（Bc）、立枯丝核菌（Rs）和辣椒炭疽菌（Cc）等植物病原真菌的EC 50均小于1 μ g/mL。进一步的生物活性测定表明，化合物6 u对水稻赤霉病和水稻纹枯病的防治效果与多菌灵相当。3D-QSAR模型揭示了吡咯1位上的大体积给电子基团、苯环4位上的大体积吸电子基团和碳酸酯基上的小分子烷基对目标化合物抗Rs活性的关键影响。在化合物6 u处理下，菌丝形态异常，孢子萌发延迟。鉴于目标化合物具有优异的广谱抗真菌作用，我们由衷地期待上述发现能够激发高效抗真菌先导化合物的发现，这些先导化合物可能对植物病原真菌具有创新的作用机制。
Aiming to discover novel high-efficient antifungal leads that possess an innovative action mechanism, twenty-three carboxylated pyrroline-2-one derivatives, bearing a phenylhydrazine moiety, were rationally designed and firstly prepared in this letter. The in vitro bioassays showed that most of the compounds possessed excellent antifungal effects with the EC50 values of less than 1 mu g/mL against the phytopathogenic fungi Fusarium graminearum (Fg), Botrytis cinerea (Bc), Rhizoctonia solani (Rs) and Colletotrichum capsici (Cc). The further bioassays showed that the compound 6u showed the comparable in vivo control effect with carbendazim against fusarium head blight and rice sheath blight. The 3D-QSAR model revealed the pivotal effects of a bulky electron-donating group at the 1-position of pyrrolering, a bulky electron-withdrawing group at the 4-position of phenyl ring and a small alkyl at the carbonate group on the anti-Rs activities of target compounds. The abnormal mycelial morphology and delayed spore germination were observed in the treatments of compound 6u. Given the excellent and broad-spectrum antifungal effects the target compounds have, we unfeignedly anticipated that the above finding could motivate the discovery of high-efficient antifungal leads, which might possess an innovative action mechanism against phytopathogenic fungi.