3-取代硫基-4-N-取代邻羟苯基亚胺基-5-乙基-1,2,4-三唑类化合物的合成、抗菌活性及分子模拟

Synthesis,molecular simulation and antibacterial activity of 3-substituted sulfur-4-N-(2-substituted hydroxyphenyl)imino-5-ethyl-1,2,4-triazole

本文将具有良好生物活性的三唑环、-N=CH-以及-NH-COCH2-等片段引入同一分子中,设计、合成6个新型3-取代硫基-4-N-取代邻羟苯基亚胺基-5-乙基-1,2,4-三唑类化合物(a^f),并通过核磁共振波谱(NMR)进行表征.生物活性测试表明目标化合物对大肠杆菌、金色葡萄球菌和白色念珠菌表现出良好的抑菌效果,对白色念珠菌的抑菌率均高于96%,特别的,化合物f对大肠杆菌和白色念珠菌的抑菌率达到100%.利用Auto Dock与Vina分子对接程序研究了目标化合物与FabI、FabH和FabB相互作用模式,结果显示目标化合物对FabI和FabB的结合自由能均优于其经典抑制剂,能依靠与FabI和FabB形成氢键及疏水作用而稳定存在于活性口袋,阻止其参与催化合成细菌脂肪酸,以达到抗菌的目的.分子对接结合自由能与抗菌活性测试表现的效果相一致,可利用分子对接提高抑菌化合物设计的准确性.

In this paper,six novel 3-substituted sulfur-4-N-(2-substituted hydroxyphenyl)imino-5-ethyl-1,2,4-triazole compounds(a^f)were designed and synthesized by in-troducing triazole rings,-N =CH-and-NH-COCH2-with good biological activity into the same molecule,and it was characterized by NMR. The bioactivity test indicated that the target compound showed good bacteriostatic effect on Escherichia coli, Staphylococcus aureus and Monilia albicans, the antibacterial activity was higher than 96%. The interaction of target compounds with FabI,FabH and FabB was studied by using Auto Dock and Vina molecular docking procedure. The results showed that the target compounds scored FabI and FabB better than their classical inhibitors,compounds can be stably present in the active site by forming hydrogen bonds and hydrophobic interaction with FabI and FabB,and prevents the protease from participating in the catalytic synthesis of bacterial fatty acids for antibacterial purposes. The binding free energy score of molecular docking was consistent with the effect shown by the antibacterial activity test,so the accuracy of the design of molecular docking effective bacteriostatic compounds can be used.