Design, synthesis, antifungal activity and 3D-QSAR study of novel pyrazole carboxamide and niacinamide derivatives containing benzimidazole moiety
Design, synthesis, antifungal activity and 3D-QSAR study of novel pyrazole carboxamide and niacinamide derivatives containing benzimidazole moiety
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含苯并咪唑部分的新型吡唑甲酰胺和烟酰胺衍生物的设计、合成、抗真菌活性和3D-QSAR研究
DOI：
10.1039/c8nj05150j
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发表时间：
2019-02-21
影响因子：
3.3
通讯作者：
Yang, Chun-Long
中科院分区：
文献类型：
--
作者：
Si, Wei-Jie;Wang, Xiao-Bin;Yang, Chun-Long
设计并合成了一系列新型含苯并咪唑结构的吡唑甲酰胺和烟酰胺类抗真菌药物。所有目标化合物均通过FTIR、H-1 NMR、C-13 NMR、HRMS和元素分析等手段进行了表征。化合物T1的结构通过单晶X射线衍射分析进一步证实。采用菌丝生长抑制法测定了目标化合物对4种植物病原真菌（灰葡萄孢、立枯丝核菌、禾谷镰刀菌和早疫病链格孢）的体外抑菌活性。生物活性测定结果表明，部分化合物对B具有较好的抑菌活性。灰霉病菌在100 μ g ML-1的浓度下比其它三种真菌的浓度高。为了更好地探索构效关系（SAR），测定了目标化合物对B的EC 50值。测量并评估灰斑。采用比较分子力场分析（CoMFA）技术，以受试化合物对B的抑制活性为基础，进行了三维定量构效关系（3D-QSAR）研究。灰叶分子建模结果显示，交叉验证的q（2）和非交叉验证的r（2）值分别为0.578和0.850，具有良好的预测能力。
A series of novel pyrazole carboxamide and niacinamide derivatives containing a benzimidazole moiety were designed and synthesized as antifungal candidate agents. All target compounds were characterized by FTIR, H-1 NMR, C-13 NMR, HRMS and elemental analysis techniques. The structure of compound T1 was further confirmed by single crystal X-ray diffraction analysis. The antifungal activities of the target compounds were evaluated in vitro against four phytopathogenic fungi (namely Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum and Alternaria solani) by the mycelium growth inhibition method. The bioassay results indicated that some of the compounds exhibited good antifungal activity against B. cinerea at 100 mu g ML-1 compared to other three fungi. In order to better explore the structure-activity relationship (SAR), the EC50 values of target compounds against B. cinerea were measured and assessed. Subsequently, a 3D quantitative structure-activity relationship (3D-QSAR) study was carried out using the comparative molecular field analysis (CoMFA) technique based on the inhibitory activities of tested compounds against B. cinerea. Molecular modelling results revealed fine predictive ability with cross-validated q(2) and non-cross-validated r(2) values of 0.578 and 0.850, respectively.