7-[3-氨甲基-4-(脲亚氨基)吡咯烷-1-基]喹诺酮衍生物的合成与抗菌作用研究

目的 寻找新的喹诺酮类抗菌药.方法 设计合成7-位具有较强亲水性取代基的7个氟喹诺酮衍生物,测定其体外抗菌活性.结果 化合物10对金葡菌(包括MRSA)和表葡菌(包括MRSE)的活性(MIC:0.06～4μg/mL)与左氧氟沙星和吉米沙星基本相当.化合物11对肺炎链球菌08-2的活性(MIC:0.25μg/mL)分别是左氧氟沙星和吉米沙星的128倍和32倍,化合物12对肺炎克雷伯菌09-22和09-23的活性(MIC:1μg/mL)分别是左氧氟沙星和吉米沙星的16倍和4倍,但目标物对革兰阴性菌的活性普遍弱于对照药.结论 7-位取代基的水溶性并非决定喹诺酮抗菌活性的主要因素.

Synthesis and in vitro antibacterial activity of 7-[3-(aminomethyl)-4-(semicarbazono)pyrrolidin-1-yl] quinolone derivatives

Objective To find new antibacterial agents of quinolones with high activity. Methods Seven fluoroquinolone derivatives with more water solubility substituent at C-7 position were designed, synthesized and evaluated for their in vitro activity against seventeen Gram-positive and thirteen Gram-negative strains. Results The activity of compound 10(MIC: 0.06～4μg/mL) was comparable to levofloxacin and gemifloxacin against S. aureus including MRSA and S. epidermidis including MRSE. Compound I(MIC: 0.25μg/mL) is 32～128 fold more potent than both the reference drugs against S. pneumoniae 08-2, and compound 12(MIC: 1μg/mL) is 16 and 4 fold more potent than levofloxacin and gemifioxacin against both K. pneumoniae 09-22 and 09-23, respectively. Conclusion The water solubility of the substituent at C-7 position is not main parameter affecting antibacterial activity.