Novel 5-chloro-pyrazole derivatives containing a phenylhydrazone moiety as potent antifungal agents: synthesis, crystal structure, biological evaluation and a 3D-QSAR study
Novel 5-chloro-pyrazole derivatives containing a phenylhydrazone moiety as potent antifungal agents: synthesis, crystal structure, biological evaluation and a 3D-QSAR study
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含有苯腙部分的新型 5-氯吡唑衍生物作为有效的抗真菌剂：合成、晶体结构、生物学评价和 3D-QSAR 研究
DOI：
10.1039/c9nj00574a
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发表时间：
2019-04-28
影响因子：
3.3
通讯作者：
Yang, Chun-Long
中科院分区：
文献类型：
--
作者：
Jiao, Jian;Wang, An;Yang, Chun-Long
基于活性亚结构组合原理，设计、合成了24个含苯腙结构的5-氯吡唑衍生物，并对其抗真菌活性进行了评价。它们的结构用H-1 NMR、C-13 NMR和HR-MS谱进行了确证。用X射线衍射分析了化合物8a的单晶结构。对禾谷镰刀菌、灰葡萄孢和立枯丝核菌进行了体外抑菌活性评价。生物活性测定结果表明，大部分目标化合物具有明显的杀菌活性。化合物7 c对上述三种植物病原真菌的EC_（50）分别为0.74、0.68和0.85 g/mL。其中化合物7 c、8d和8 g具有明显的生物活性。solani，EC 50值分别为0.85、0.25和0.96 g mL（-1）。此外，CoMFA和CoMSIA分子模型用于3D-QSAR研究，并呈现出良好的预测能力，q（2）值分别为0.575和0.667，r（2）值分别为0.961和0.962。研究结果为设计和合成具有良好抗真菌活性的吡唑衍生物提供了参考。
Based on the active substructure combination principle, twenty-four novel 5-chloro-pyrazole derivatives containing a phenylhydrazone moiety were designed, synthesized, and evaluated for their antifungal activity. Their structures were confirmed using H-1 NMR, C-13 NMR, and HR-MS spectra. The single-crystal structure of compound 8a was analyzed emphatically using X-ray diffraction. The antifungal activities against Fusarium graminearum, Botrytis cinerea, and Rhizoctonia solani were evaluated in vitro. The results of the bioassays revealed that most of the target compounds showed obvious fungicidal activity. Strikingly, the compound 7c exhibited the most potent activity with EC50 values of 0.74, 0.68, and 0.85 g mL(-1) against the above three plant pathogenic fungi, respectively. The compounds 7c, 8d, and 8g showed significant bioactivity against R. solani with EC50 values of 0.85, 0.25, and 0.96 g mL(-1), respectively. In addition, CoMFA and CoMSIA molecular modeling was performed for a 3D-QSAR study, and presented a good predictive ability with q(2) values of 0.575 and 0.667, and r(2) values of 0.961 and 0.962, respectively. The results provide useful information for guiding the design and synthesis of novel potent pyrazole derivatives with good antifungal activity.