Photoinduced N-Demethylation of Rufloxacin and its Methyl Ester Under Aerobic Conditions¶

Belvedere, Alessandra; Boscá, Francisco; Cuquerella, M. Consuelo; Guidi, Guido De; Miranda, Miguel A.

doi:10.1562/0031-8655(2002)0760252pndora2.0.co2

Cited by 7 publications

(12 citation statements)

References 41 publications

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“…In the cation formed by photoinduced C‐F bond cleavage in FLE, intramolecular reaction with the N‐Et chain is prevented by the electron‐withdrawing effect of fluorine and intermolecular attack by nucleophiles is facilitated (44). Photodehalogenation seems to be the main process involved in the phototoxic effect of FQs; however, this photodegradation process is not significant in CIP, NOR (38), Moxifloxacin (MOX) (45,46), OFL (38) and RUF (32,47). For these two latter FQs, irradiation under aerobic conditions gives rise to N ‐demethylation of the piperazinyl ring via photoionization from singlet state and formation of hydrated electrons, as well as 1 O 2 generation from drug triplet excited state.…”

Section: Fq Photochemistry and Photophysics An Overviewmentioning

confidence: 99%

“…A cooperative Type‐I and ‐II mechanism was reported for RUF (64). Besides, H 2 O 2 , an unstable product of FQs photolysis (47), can react with traces of metal ions in order to promote the formation of the OH • radical via Haber–Weiss reaction, resulting in DNA base oxidation and strand cleavage (57,58). In parallel, the O 2 −• formed by drug photoionization could be able to extract a hydrogen atom from the sugar moiety that also results in cleavage of the duplex (58).…”

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confidence: 99%

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Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

Guidi

Bracchitta

Catalfo

2011

Photochem & Photobiology

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This review focuses on damage photosensitized by the fluoroquinolone (FQ) antibacterial drugs. Different models are employed to study biosubstrate photodamage mediated by FQs (organisms, cells, isolated biomolecules and super molecules). Being that the effect of environment (polarity of the medium, ions, pH, binding with bio-molecules, etc.) is crucial in FQ photochemistry, photobiological reactions can be consequently dramatically influenced. Thus, the photosensitization processes induced by FQs are here discussed taking into account that such extensive and cross-targeted pathological implications request an excursus covering photosensitization in systems of increasing molecular complexity. In vivo and in vitro evidences for photoallergy, phototoxicity, photomutagenesis and photocarcinogenesis mediated by FQs are discussed.

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Section: Fq Photochemistry and Photophysics An Overviewmentioning

confidence: 99%

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confidence: 99%

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

Guidi

Bracchitta

Catalfo

2011

Photochem & Photobiology

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“…Two primary processes are involved: photoionization from 1 RFX and singlet oxygen generation from 3 RFX. 49 Drug mediated photosensitization on free bases and, to a lesser extent, on native DNA, induces photodamage largely by photooxidation, as confirmed by a quantitative evaluation of the marker compounds (indicative of the two main mechanisms of photosensitization). The prevalence of the type II pathway in the photooxidative sensitization mechanism of RFX is also supported by the determination of the rate constants involved, which allowed a quantification of the competition between the two mechanisms.…”

Section: Introductionmentioning

confidence: 78%

“…The determination of H 2 O 2 was carried out according to literature with some modifications. 49 Immediately after irradiation, the cells were removed from the 1 mL aliquot of the above sample by means of centrifugation at 13000 g for 1 min. The solution was then rapidly mixed with 500 lL H 2 SO 4 0.2 M and with 500 lL of 1.6 mM ammonium iron(II) sulfate.…”

Section: Extracellular H 2 O 2 and Hcho Determinationmentioning

confidence: 99%

“…The molecular mechanism of RFX photodegradation under aerobic conditions has been studied. 49 This process leads to the formation of a principal photoproduct, an N-demethylated, with hydrogen peroxide (H 2 O 2 ) and formaldehyde (HCHO) as side products. Two primary processes are involved: photoionization from 1 RFX and singlet oxygen generation from 3 RFX.…”

Section: Introductionmentioning

confidence: 99%

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Rufloxacin-induced photosensitization in yeast

Catalfo

Calandra

Renis

et al. 2007

Photochem Photobiol Sci

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The fluoroquinolone Rufloxacin (RFX) is active as specific inhibitor of bacterial gyrase. The adverse effects of the photosensitization induced by fluoroquinolones are well known. A predominant type II photosensitizing activity of Rufloxacin has already been demonstrated on simpler models (free nucleosides, calf thymus DNA), whereas a cooperative mechanism was corroborated on more complex ones (plasmid and fibroblast). The purpose of this study is to examine the drug photocytoxicity in another complex cellular model, a wild-type eukaryotic fast-growing microorganism whose cultivation is cheap and easily managed, Saccharomyces cerevisiae. This work represents the first report of the potential photogenotoxicity of Rufloxacin. Particular emphasis was given to DNA modifications caused in yeast by the formation of Rufloxacin photomediated toxic species, such as hydrogen peroxide and formaldehyde. Drug phototoxicity on yeast was evaluated by measuring DNA fragmentation (single/double strand breaks) using single cell gel electrophoresis assay and 8-OH-dGuo, a DNA photooxidation biomarker, by HPLC-ECD. Cellular sensitivity was also assessed by cell viability test. The extra- and intracellular RFX concentration (as well as its main photoproduct) was verified by HPLC-MS, whereas the cytotoxic species were evaluated by colorimetric assays. The results confirm the phototoxicity of Rufloxacin on yeast cell and are in agreement with those previously obtained with human fibroblast and with simpler models used recently, and provide a clear link between DNA photosensitization and overall phototoxicity.

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Photochemistry of the Phototoxic Drug Lomefloxacin: Paths Observed in the Presence of Amines or NaOH and from the Methyl Ester

Fasani¹,

Mella²,

Albini³

2004

Eur J Org Chem

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The photochemistry of the fluoroquinolone drug lomefloxacin has been examined in aqueous solution in the presence of aliphatic amines (0.01 and 0.2 M) as well as 0.01 M NaOH; a fairly efficient decomposition (Φ = 0.2 to 0.4) takes place. Under the above conditions the product distribution is the same and differs from that previously observed in neutral and acidic aqueous solution. Five products have been characterized, all of them resulting from reductive elimination of the fluorine in the 8‐position and some alteration of the piperazine side‐chain. All of the products are rationalized as resulting from the heterolytic cleavage of the C8−F bond in triplet lomefloxacin to give the corresponding triplet aryl cation. Due to the multiplicity, the C8 site has a carbene rather than a localized cation character. Under these conditions — the amino group in the 4′‐position is free — the main process is formal hydride transfer from the 3′‐position and the minor one attack of the 4′‐amino group at the C6−F bond. In accordance with this rationalization, the methyl ester of lomefloxacin exhibits a closely analogous photochemistry under neutral conditions. The cationic intermediate may be involved in the observed phototoxicity of the drug, via an oxygen‐independent path. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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Photoinduced N-Demethylation of Rufloxacin and its Methyl Ester Under Aerobic Conditions¶

Cited by 7 publications

References 41 publications

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

Rufloxacin-induced photosensitization in yeast

Photochemistry of the Phototoxic Drug Lomefloxacin: Paths Observed in the Presence of Amines or NaOH and from the Methyl Ester

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