Synthesis and antibacterial evaluation of certain quinolone derivatives.
A number of 7-substituted quinolone derivatives were synthesized and evaluated for antibacterial and cytotoxic activities. Preliminary results indicated that most compounds tested in this study demonstrated better activity against methicillin-resistant Staphylococcus aureus than norfloxacin. Among them, 1-(4-amino-2-fluorophenyl)-6-fluoro-1,4-dihydro-7-[4-[2-(4-methoxyphenyl)-2-hydroxyiminoethyl]-1-piperazinyl]-4-oxo-3-quinolinecarboxylic acid (11d) and its ketone precursor 10d exhibited significant activities against Klebsiella pneumoniae, methicillin-resistant S. aureus, erythromycin- and ampicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis. Due to strong cytotoxicities of 11d (a mean log GI(50) of -5.40), compound 10d, with good antibacterial activities and low cytotoxicities (a mean log GI(50) of -4.67), is a more potential drug candidate.
Chen
Y L
YL
School of Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan, Republic of China. yeloch@cc.kmu.edu.tw
Fang
K C
KC
Sheu
J Y
JY
Hsu
S L
SL
Tzeng
C C
CC
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004352:Drug Resistance, Microbial; D013293:Enterococcus faecalis / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013210:Staphylococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
C430904:1-(4-amino-2-fluorophenyl)-6-fluoro-1,4-dihydro-7-(4-(2-(4-methoxyphenyl)-2-oxoethyl)-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid; D000900:Anti-Bacterial Agents; D010879:Piperazines; D015363:Quinolones