Synthesis, antibacterial, and cytotoxic evaluation of certain 7-substituted norfloxacin derivatives.
We report herein the synthesis and biological evaluation of two series of 7-substituted norfloxacin derivatives. Most compounds tested in this study demonstrated better activity against methicillin-resistant Staphylococcus aureus than norfloxacin. Preliminary in vitro evaluation indicated that the 7-[4-(2-hydroxyiminoethyl)piperazin-1-yl] derivatives 3b-e possess distinct cytotoxicity profiles as compared with their alpha-methylene-gamma-butyrolactone counterparts, 4b,e: i.e., excellent activities against the renal cancer subpanel. Among them, 1-ethyl-6-fluoro-7-¿4-[2-(4-chlorophenyl)-2-hydroxyiminoethyl]-1-p ipe razinyl¿-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (3d) demonstrated the most significant activities against renal cancer cell lines, with log GI(50) values of -6.40 against CAK-1, -6.14 against RXF 393, and -7.54 against UO-31, compared with a mean log GI(50) value of -5.03.
Fang
K C
KC
School of Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan, Republic of China.
Chen
Y L
YL
Sheu
J Y
JY
Wang
T C
TC
Tzeng
C C
CC
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D004352:Drug Resistance, Microbial; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C415187:1-ethyl-6-fluoro-7-(4-(2-(4-chlorophenyl)-2-hydroxyiminoethyl)-1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D010879:Piperazines; D015363:Quinolones; D009643:Norfloxacin