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多药耐药菌的频繁出现已日益严重威胁人类健康,开发结构新型的抗菌药物已成为全世界战胜耐药菌的重要课题.本文设计合成了一系列具有抗微生物潜力的酰腙桥链的喹唑酮咪唑类新化合物,其结构经核磁共振氢谱(~1H NMR)、核磁共振碳谱(~(13)C NMR)和高分辨质谱(HRMS)进行表征.生物活性研究发现,一些目标化合物具有较好的抗微生物活性,特别是十八烷基衍生物6h和4-氟苄基取代的化合物7i,抗痢疾杆菌和大肠杆菌DH52的活性是氯霉素的2.5~3.3倍,抗黄曲霉菌活性是临床药物氟康唑的28和8.4倍.用紫外-可见光谱法进行了高活性化合物7i靶向DNA的初步研究,发现咪唑衍生物7i可嵌入小牛胸腺DNA形成7i-DNA超分子络合物,从而阻断DNA复制,展现出较好的抗细菌活性.分子模拟研究表明,活性分子7i与DNA碱基通过氢键结合.该类化合物作为新型抗真菌黄曲霉菌专一特效药及新型抗细菌药值得深入研究.
The frequent emergence of multidrug-resistant bacteria has become a serious threat to human health and the development of a new type of antibacterial drug has become an important issue in the fight against drug-resistant bacteria in the world.This paper designed and synthesized a series of quinacridone- Their structures were characterized by ~ 1 H NMR, ~ 13 C NMR and HRMS. The bioactivities of some of the target compounds, The activity of anti-dysentery bacillus and E.coli DH52 with good antimicrobial activities, especially octadecyl derivatives 6h and 4-fluorobenzyl substituted compounds, was 2.5-3.3 times that of chloramphenicol, Mycotic activity was 28 and 8.4 times that of the clinical drug fluconazole.It was found that the 7i-DNA supermolecule could be embedded in calf thymus DNA by imidazole derivative 7i by ultraviolet-visible spectroscopy Complex, thus blocking DNA replication, showing good antibacterial activity.Model simulation studies have shown that the active molecule 7i and DNA bases through hydrogen bonding.These compounds as a new antifungal Aspergillus flavus-specific drug And new anti-bacteria Worthy of further study.