新型2,4,6-三取代嘧啶衍生物作为琥铂酸脱氢酶抑制剂的研究（英文）

发布时间：2022-10-22 18:20

　　设计并合成了36个未见文献报道的嘧啶类衍生物,并用IR、1HNMR、13CNMR和HRMS对其结构进行了表征.以5种植物病原真菌即水稻纹枯、小麦赤霉、玉米小斑、油菜菌核和番茄灰霉病菌为靶标,对合成化合物的抑菌活性进行了测定.结果显示,在20 mg/L时,其中的大多数都有着显著的抑菌活性.其中,化合物2-甲基-4-（呋喃-2-基）-6-（对甲苯基）嘧啶（2c）和2-（1-吡唑-1-基）-4-（4-氯苯基）-6-（5-甲基呋喃-2-基）嘧啶（3d）对油菜菌核的抑制活性最强,其EC50值分别为0.072、0.077 mg/L,与市售杀菌剂氟吡菌酰胺（EC50=0.244 mg/L）相比,具有更好的抑菌活性.与此同时,还测定了化合物2c和3d对琥珀酸脱氢酶（SDH）的抑制活性.结果表明,它们的半数抑制浓度（IC50）分别为0.115和0.121mg/L,也比氟吡菌酰胺（IC50=0.356 mg/L）有更好的抑制活性.分子对接研究结果显示,化合物2c、3d和氟吡菌酰胺与SDH的结合能分别为-32.2,-31.8和-28.9 kJ/mol,这表明它们对SDH的亲和力比氟吡菌酰胺更强.化合物2c和... 

【文章页数】：12 页

【文章目录】：
1 Introduction
2 Results and discussion
    2.1 Chemistry
    2.2 Antifungal activity
    2.3 Inhibitory activity against enzyme
    2.4 Homology modelling and molecular docking analysis
3 Conclusions
4 Experimental section
    4.1 General
    4.2 Synthesis of target compounds
        4.2.1 Synthesis of intermediate 1
        4.2.2 Synthesis of target compounds 2a～2l
        4.2.3 Synthesis of target compounds 3a～3l
        4.2.4 Synthesis of target compounds 4a～4l
    4.3 Antifungal assay
    4.4 Assay of enzyme inhibition activity
        4.4.1 Isolation of SDH from S.sclerotiorum
        4.4.2 Succinate:ubiquinone/2,6-dichloro-4-[(4-hydroxyphenyl)imino]-2,5-cyclohexadien-1-one (DCPIP) activity inhibition
    4.5 Homology modeling and molecular docking
        4.5.1 Homology modeling
        4.5.2 Molecular docking


【参考文献】：
期刊论文
[1]Synthesis and biological evaluation of novel pyrazole carboxamide with diarylamine-modified scaffold as potent antifungal agents[J]. Xiao-Xiao Zhang,Hong Jin,Yuan-Jie Deng,Xu-Heng Gao,Yong Li,Yong-Tian Zhao,Ke Tao,Tai-Ping Hou.  Chinese Chemical Letters. 2017(08)



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