氟喹诺酮-蛇床子素杂合体的合成与抗菌活性

Synthesis and antibacterial activities of fluoroquinolone- osthole hybrids

摘要:

运用杂合抗菌策略，将氟喹诺酮类抗菌剂与天然产物蛇床子素杂合，设计合成系列杂合抗菌体。目标化合物经1HNMR、13CNMR和元素分析确认结构。采用二倍稀释法进行抗菌活性测试，结果显示：该类杂合体对所测细菌有较好抑制作用，以化合物1-环丙基-6-氟-7-(3-甲基-4-(2-((8-(3-甲基丁-2-烯-1-基)-2-氧代-2H-色烯-7-基)氧)乙基)哌嗪-1-基)-4-氧代-1,4-二氢喹啉-3-羧酸（Ⅳf）的活性最为突出，对金黄色葡萄球菌（S. aureus）、大肠杆菌（E. coli）、绿脓杆菌（P. aeruginosa）和耐甲氧西林金黄色葡萄球菌（MRSA）和耐氟喹诺酮大肠杆菌（FREC）的最小抑菌浓度（MIC）分别为0.125、2、2、2和4 μg/mL，优于对照药诺氟沙星 ，可作为抗菌候选化合物进一步研究，该杂合抗菌体具有抗菌增效作用和协同效应，可能与作用于多个靶标有关。

Abstract:

Using a hybrid antibacterial strategy, a series of hybrid antibacterial agents were designed and synthesized by hybridizing fluoroquinolone antibiotics with osthole. The structure of the target compounds were confirmed by 1HNMR, 13CNMR and elemental analysis. The antibacterial activities were tested using the double dilution method, the results showed that these hybrid agents had a good inhibitory effect on the tested bacteria, and 1-cyclopropyl-6-fluoro-7-(3-methyl-4-(2-((8-(3-methylbut-2-en-1-yl)-2-oxo-2H- chromen-7-yl)oxy)ethyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid(IVf) exhibited significant antibacterial activitiies, with the minimum inhibitory concentrations(MIC) against Staphylococcus aureus(S. aureus), Escherichia coli(E. coli), Pseudomonas aeruginosa(P. aeruginosa), methicillin-resistant S. aureus(MRSA) and fluoroquinolone resistant E. coli(FREC) was 0.125, 2, 2, 2 and 4 μg/mL, respectively, which was superior to the control drug norfloxacin and could be further studied as an antibacterial candidate compound. The hybrid antibacterial agents have antibacterial enhancing and synergistic effects, which may be related to acting on multiple targets.