Synthesis, primary photophysical and antibacterial properties of naphthyl ester cinoxacin and nalidixic acid derivatives.
We have synthesized two naphthyl ester quinolone derivates and determined their ability to generate reactive oxygen species (ROS) such as (1)O(2), ()OH, H(2)O(2) upon photolysis with UV-A light. The ability of cinoxacin (1) and nalidixic acid (2), and their naphthyl ester derivatives (3 and 4) to generate a dose-dependent amount of singlet oxygen and ROS (()(-)O(2), ()OH) in cell-free systems was detected by histidine assay and by luminol-enhanced chemiluminescence (LCL), respectively. Their electronic absorption and emission spectra were quantified and their photostability was determined. Their tendency to generate peroxidic derivative species showed the following order: 3>4; in contrast, their ability to generate singlet oxygen was 4>3 and these were better sensitizers than their parent quinolones 1 and 2. The antibacterial activity in darkness and under irradiation of compounds 3 and 4 was tested on Escherichia coli and compared with that of their parent compounds. An enhanced antibacterial activity by irradiation of the naphthyl esters of cinoxacin and nalidixic acid on E. coli was observed.
Laboratorio de Fotoquímica, Centro de Química, Instituto Venezolano de Investigaciones Científicas I.V.I.C., Apartado 21827, Caracas 1020-A, Venezuela. fvargas@ivic.ve
Franklin
F
Vargas
Tamara
T
Zoltan
Carlos
C
Rivas
Alvaro
A
Ramirez
Tulynan
T
Cordero
Yrene
Y
Díaz
Carla
C
Izzo
Ylec M
YM
Cárdenas
Verónica
V
López
Lubimar
L
Gómez
Jessenia
J
Ortega
Alberto
A
Fuentes
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival; D002937:Cinoxacin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D017665:Hydroxyl Radical / Q000737:chemistry / Q000378:metabolism; D009268:Nalidixic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009287:Naphthyridines; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism
C532799:1-ethyl-1,4-dihydro-4-oxo-(1,3)dioxolo(4,5-g)cinnoline-3-napthyl ester; C532800:1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-naphthyl ester; D000900:Anti-Bacterial Agents; D009281:Naphthalenes; D009287:Naphthyridines; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D009268:Nalidixic Acid; D002937:Cinoxacin; D010100:Oxygen