Photostability and biological activity of fluoroquinolones substituted at the 8 position after UV irradiation

Abstract

Q-35 [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methylaminopiperidine-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.

Chemiluminescence Determination of Balofloxacin Based on Europium (III)-Sensitized KBrO3-Na2S2O4Reaction in Micellar Medium

“…[1][2][3] The methoxy group at the 8-position reduces photoallergic responses. 4,5 Like other new fluoroquinolones, the bactericidal action of BLFX results from inhibition of the eneymes topoisomerase (II) (DNA gyrase) and topoisomerase (IV). 6 It was largely excreted via urine as the unchanged chemical constitution.…”

Combined Use of In Vitro Phototoxic Assessments and Cassette Dosing Pharmacokinetic Study for Phototoxicity Characterization of Fluoroquinolones

“…1). FQs, antibacterials, are well recognized to be a phototoxic chemical series (14), and the structure-phototoxicity relationships of FQs have been reported (15,16); substitution groups at the eight position play a key role on the phototoxic potential of FQs. Thus, the tested FQs were divided into three groups based on the substituent at the eight position of FQs in the present study, namely, free (NFLX and CPFX), nonhalogenated (LVFX and GFLX), and halogenated (LFLX and SPFX) groups.…”

Photostability studies on gemifloxacin and lomefloxacin in bulk powder and dosage forms

“…On the other hand, a hydrogen group at position 8 provides a FQ molecule with only a mildly phototoxic potential [9][10][11][12]. UV irradiation of 8-halogenoquinolones has been reported to cause photoinstability [13][14][15][16]. FQ derivatives with a methoxy group at position 8, such as gatifloxacin and moxifloxacin, have been demonstrated to be the most photostable and the least phototoxic [1].…”