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Research Article

活性二氮烯基支架作为抗微生物药物发现必需靶标抑制剂的分子对接研究

卷 20, 期 15, 2019

页: [1587 - 1602] 页: 16

弟呕挨: 10.2174/1389450120666190618122359

价格: $65

摘要

背景：据报道，二氮烯基化合物（-N = N-键）具有抗菌活性。在现代药物发现中，通常通过分子对接研究来探索药物-受体的相互作用。 材料与方法：筛选了三类二氮烯基支架进行对接研究，以探索与各种微生物靶标相互作用的结合机制。二氮烯基席夫碱（SBN-20，SBN-21，SBN-25，SBN-33，SBN-39，SBN-40和SBN-42），萘酚药效基二氮烯基席夫碱（NS-2，NS-8，NS -12，NS-15，NS-21和NS-23），基于吗啉的二氮烯基查耳酮（MD-6，MD-9，MD-14，MD-16，MD-20和MD-21）对接与不同标准药物相比，各种细菌和真菌蛋白。此外，通过Schrodinger软件的QikProp模块预测了这些分子的药物相似性和ADME性质。 结果：与之相比，大多数衍生物对细菌蛋白的对接得分和结合能更低，例如二氢蝶呤合酶（PDB：2VEG），氨基葡萄糖6-磷酸合酶（PDB：2VF5），二氢叶酸还原酶（PDB：3SRW）。标准药物。预测基于萘酚的二氮烯基席夫碱NS-21和NS-23对参与固醇生物合成的细胞色素P450固醇14-α-脱甲基酶（CYP51）（PDB：5FSA）起作用，抗真菌药物是必需的靶标。与标准药物环丙沙星相比，衍生物MD-6，NS-2，NS-21和NS-23对细菌DNA拓扑异构酶（PDB：3TTZ）表现出较高的对接分数。此外，大多数合成衍生物已显示出类似药物的特征。 结论：因此，这些化合物可作为有效的DNA拓扑异构酶抑制剂开发为新型抗菌剂，并作为CYP51抑制剂开发为抗真菌剂。

关键词: 二氮烯基，吗啉，萘酚，席夫碱，对接分数，二氢蝶呤合酶。

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