98079-47-1Relevant articles and documents
Seeking the mechanism responsible for fluoroquinolone photomutagenicity: A pulse radiolysis, steady-state, and laser flash photolysis study
Soldevila, Sonia,Consuelo Cuquerella,Lhiaubet-Vallet, Virginie,Edge, Ruth,Bosca, Francisco
, p. 417 - 425 (2015/02/19)
The mechanism responsible for the remarkable photomutagenicity of fluoroquinolone (FQ) antibiotics remains unknown. For this reason, it was considered worthwhile to study in detail the interactions between DNA and a dihalogenated FQ such as lomefloxacin (LFX; one of the most photomutagenic FQs) and its N-acetyl derivative ALFX. Studies of photosensitized DNA damage by (A)LFX, such as formation of DNA single-strand breaks (SSBs), together with pulse radiolysis, laser flash photolysis, and absorption and fluorescence measurements, have shown the important effects of the cationic character of the piperazinyl ring on the affinity of this type of drug for DNA. Hence, the formation of SSBs was detected for LFX, whereas ALFX and ciprofloxacin (a monofluorated FQ) needed a considerably larger dose of light to produce some damage. In this context, it was determined that the association constant (Ka) for the binding of LFX to DNA is ca. 2×103 M-1, whereas in the case of ALFX it is only ca. 0.5×103 M-1. This important difference is attributed to an association between the cationic peripheral ring of LFX and the phosphate moieties of DNA and justifies the DNA SSB results. The analysis of the transient species detected and the photomixtures has allowed us to establish the intermolecular processes involved in the photolysis of FQ in the presence of DNA and 2'-deoxyguanosine (dGuo). Interestingly, although a covalent binding of the dihalogenated FQ to dGuo occurs, the photodegradation of FQ...DNA complexes did not reveal any significant covalent attachment. Another remarkable outcome of this study was that (A)LFX radical anions, intermediates required for the onset of DNA damage, were detected by pulse radiolysis but not by laser flash photolysis.
Photoinduced C-F bond cleavage in some fluorinated 7-amino-4-quinolone- 3-carboxylic acids
Fasani,Barberis Negra,Mella,Monti,Albini
, p. 5388 - 5395 (2007/10/03)
The photochemistry of some fluorinated 7-amino-4-quinolone-3-carboxylic acids used in therapy as antibacterials and known to be phototoxic has been investigated in water. All of them undergo heterolytic defluorination, and this appears to be a path for the generation of aryl cations in solution. 6- Fluoro derivatives such as norfloxacin (Φ(dec) = 0.06) and enoxacin (Φ(dec) = 0.13) give the corresponding phenols. Insertion of an electron-donating substituent makes defluorination inefficient; thus, ofloxacin, an 8-alkoxy derivative, is found to be rather photostable (Φ(dec) = 0.001) and reacts in part via a process different from defluorination (degradation of the N-alkyl side chain). With a 6,8-difluoro derivative, lomefloxacin, the reaction is more efficient (? = 0.55) and selective for position 8. Contrary to the previous cases, the aryl cation undergoes insertion in the neighboring N- ethyl group rather than solvent addition (a carbene-like chemistry). With all of the above fluoroquinolones an intensive triplet-triplet absorption is detected and is quenched by sulfite (k(q) = (1-5) x 108 M-1 s-1). Under this condition, reductive defluorination via the radical anion takes place. The relation of the above chemistry to the phototoxicity of these drugs is commented upon briefly.
