齐多夫定衍生物的合成及抗菌活性研究  

Synthesis and antibacterial of novel zidovudine derivatives

作　　者：李锡勇 孙亚敏 姜玉钦[2] Li Xiyong;Sun Yamin;Jiang Yuqin(Weihai Marine vocational college,Weihai,264300,China;School of Chemistry and Chemical Engineering,Henan normal university,Xinxiang 453007,China)

机构地区：[1]威海海洋职业学院,山东威海264300 [2]河南师范大学化学化工学院,河南新乡453007

出　　处：《河南师范大学学报（自然科学版）》2018年第6期68-73,共6页Journal of Henan Normal University(Natural Science Edition)

基　　金：河南省重点科技攻关(152102210285);河南省产学研项目(142107000081)

摘　　要：二氢叶酸还原酶是细菌存活所必需的酶,且在哺乳动物中的氨基酸序列存在显著差异,DNA结构同源性很小,因此这些酶可以作为抗细菌感染的优秀药物靶标.为了寻找新型抗菌化合物,以齐多夫定为先导物,分别和不同取代基的芳香类的末端炔发生反应,利用药物拼合原理,将活性基团引入到目标产物结构中,得到一系列齐多夫定链接1,2,3-三氮唑的新化合物,结构经~1 H NMR,^(13) C NMR和HRMS确证.对合成化合物进行初步生物活性测试,部分化合物对化脓链球菌显示抑制作用.Dihydrofolate reductase is a necessary enzyme for the survival of bacteria,which could be used as an excellent drug target against bacterial infection due to its significant differences in the amino acid sequences in mammals and small DNA structure homology. Aiming to find new potent antibacterial compounds,zidovudine was used as a leader compound to react with different aminopropyne respectively. By using the principle of drug combination, a serials of novel 1,2,3-triazole derivatives incorporate 3＇-deoxythymidine were designed, synthesized and characterized. The target compounds were obtained using propargyl bromide and substituted aniline as starting materials followed by an azide-alkyne cycloaddition with 3＇-Azido-3＇-deoxythymidine. Antibacterial activity against streptococcus pyogenes and staphylococcus albus of all the synthesized compounds was evaluated using doxycycline as reference drugs.

关 键 词：二氢叶酸还原酶 齐多夫定 1 2 3-三氮唑 抗菌 

分 类 号：R914.5[医药卫生—药物化学]