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...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2000-10, Vol.43 (20), p.3809-3812
Main Authors: Fang, Kuo-Chang, Chen, Yeh-Long, Sheu, Jia-Yuh, Wang, Tai-Chi, Tzeng, Cherng-Chyi
Format: Article
Language:English
Subjects:
Anti-Infective Agents - chemical synthesis
Anti-Infective Agents - chemistry
Anti-Infective Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Bacteria - drug effects
Biological and medical sciences
Drug Resistance, Microbial
Drug Screening Assays, Antitumor
Humans
Medical sciences
Microbial Sensitivity Tests
Norfloxacin - analogs & derivatives
Norfloxacin - chemical synthesis
Norfloxacin - chemistry
Norfloxacin - pharmacology
Pharmacology. Drug treatments
Piperazines - chemical synthesis
Piperazines - chemistry
Piperazines - pharmacology
Quinolones - chemical synthesis
Quinolones - chemistry
Quinolones - pharmacology
Structure-Activity Relationship
Tumor Cells, Cultured
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Summary: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 α-methylene-γ-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-piperazinyl}-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (3d) demonstrated the most significant activities against renal cancer cell lines, with log GI50 values of −6.40 against CAK-1, −6.14 against RXF 393, and −7.54 against UO-31, compared with a mean log GI50 value of −5.03.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm000153x