Photostability and biological activity of fluoroquinolones substituted at the 8 position after UV irradiation.
Q-35 [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methylaminopiperid ine-1-yl)-4-oxoquinoline-3-carboxylic acid], a fluoroquinolone, has absorbance peaks at 333 and 286 nm. No spectral change was observed even when this aqueous solution was irradiated with 3 J of long-wavelength UV light (UVA) per cm2. On the other hand, its derivatives, which are unsubstituted (8-H analog) or which are substituted with fluorine at the 8 position (8-F analog), were found to have decreased antibacterial activities with a simultaneous increase in their cytotoxicities when they were degraded in a dose-dependent manner with respect to UVA irradiation. Similar results were observed with the other available fluoroquinolones. Enoxacin and lomefloxacin exposed to 0.3 J of irradiation per cm2 and norfloxacin, ofloxacin, and ciprofloxacin exposed to 1 J of irradiation per cm2 underwent absorption spectrum changes, an accompanying decrease in antibacterial activity, and an increase in cytotoxic activity. These results suggest that the introduction of a methoxy group into the 8 position of quinolones plays an important role in the stability of fluoroquinolones against irradiation by UV light.
Matsumoto
M
M
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Kojima
K
K
Nagano
H
H
Matsubara
S
S
Yokota
T
T
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D001419:Bacteria / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D024841:Fluoroquinolones; D051379:Mice; D008826:Microbial Sensitivity Tests; D010777:Photochemistry; D015363:Quinolones / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C077155:balofloxacin