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为了筛选得到对稻瘟病菌Magnaporthe grisea具有较高抑菌活性的新型化合物,根据稻瘟病菌中1,3,8-三羟基萘还原酶(3HNR)的结构信息,设计合成了系列2-硝基-1-芳乙烯(2a~2e)和2-溴-2-硝基-1-芳乙烯(3a,3b)目标化合物,并测试了其对3HNR和稻瘟病菌的抑制活性,同时运用分子对接方法对目标化合物与3HNR可能的结合模式进行了分析。结果表明:大部分目标化合物对3HNR都有很好的抑制作用(IC50<5.0μmol/L),其中,化合物3的抑制活性最好,IC_(50)值为0.53μmol/L。在50μg/m L下,目标化合物对稻瘟病菌的生长具有不同程度的抑制作用,其中2e、3a和3b的抑制率高于96%;3a和3b的EC_(50)值分别为16.4和11.6μg/m L。分子对接方法分析结果表明,硝基苯乙烯骨架结构与稻瘟病菌的3HNR活性空腔的氨基酸残基有较好的相互作用,其中化合物3中的溴原子可与3HNR中Tyr223和Tyr178的羟基形成氢键,从而解释了化合物3对3HNR有较好抑制作用的原因。
In order to screen a novel compound with high antibacterial activity against Magnaporthe grisea, a series of 2-nitro (3HNR) derivatives were designed and synthesized based on the structural information of 1,3,8-trihydroxynaphthalene reductase (3HNR) in Magnaporthe grisea (2a ~ 2e) and 2-bromo-2-nitro-1-a-vinylidene (3a, 3b) were synthesized and their inhibitory activities against 3HNR and Magnaporthe grisea were tested. Methods The possible binding modes of target compounds and 3HNR were analyzed. The results showed that most of the target compounds had a good inhibitory effect on 3HNR (IC50 <5.0μmol / L), of which compound 3 had the best inhibitory activity and IC 50 value of 0.53μmol / L. The target compounds inhibited the growth of Magnaporthe grisea at different concentrations at 50μg / m L, of which the inhibitory rates of 2e, 3a and 3b were higher than 96%. The EC 50 values of 3a and 3b were 16.4 and 11.6, respectively μg / m L. The results of molecular docking showed that there was a good interaction between the nitro-styrene framework and amino acid residues in the 3HNR active cavity of Magnaporthe grisea, in which the bromine atom in compound 3 could form with the hydroxyl groups of Tyr223 and Tyr178 in 3HNR Hydrogen bond, which explains why compound 3 has a good inhibitory effect on 3HNR.