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借助杂合体药物和多靶点药物的设计方法,将含有3-芳基-2(5H)-呋喃酮结构单元的酪氨酰t-RNA合成酶抑制剂与氟喹诺酮(DNA促旋酶抑制剂)相融合,设计合成了7个结构全新的3-芳基-2(5H)-呋喃酮-氟喹诺酮杂合体化合物.体外抗菌活性筛选发现,大多数化合物对革兰氏阳性菌、革兰氏阴性菌以及真菌均具有较好抑制作用.酶活性评价和分子模拟研究表明,该类化合物是通过干扰蛋白质合成和DNA复制来发挥抑菌作用的双重抑制剂.这些结果充分说明,3-芳基-2(5H)-呋喃酮-氟喹诺酮杂合体化合物作为抗菌化合物有进一步研究的价值.
With the design of heterozygous drugs and multi-target drugs, tyrosyl t-RNA synthetase inhibitors containing 3-aryl-2 (5H) -furanone structural units were coupled with fluoroquinolones (DNA gyrase inhibitors ) Were synthesized and seven novel 3-aryl-2 (5H) -furanone-fluoroquinolone hybrids were designed and synthesized.The antibacterial activity of the compounds was studied in vitro.It was found that most of the compounds were active against Gram-positive bacteria, Negative bacteria and fungi.Analyses of enzymatic activity and molecular simulation show that these compounds are dual inhibitors of antibacterial activity by interfering with protein synthesis and DNA replication.These results fully demonstrate that 3-aryl -2 (5H) - furanone - fluoroquinolone hybrid compounds as antimicrobial compounds for further study.