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Photosensitization by antitumor agents 2: anthrapyrazole-photosensitized oxidation of ascorbic acid and 3,4-dihydroxyphenylalanine.

A novel anthrapyrazole anticancer agent has been examined for photosensitizing properties. Illumination of the anthrapyrazole and ascorbic acid with blue light in aerated aqueous solutions causes SOD and catalase-sensitive oxygen consumption, indicating involvement of both superoxide radical and hydrogen peroxide in this process. Electron paramagnetic resonance showed that the ascorbyl radical is also produced during the photooxidation. When 3,4-dihydroxyphenylalanine (Dopa) is used as a substrate, production of hydrogen peroxide is evidenced by catalase-sensitive oxygen consumption. Generation of hydroxyl radicals during illumination of the drug and ascorbic acid (or Dopa) in the presence of catalytic amounts of the Fe(III)/EDTA complex is demonstrated using EPR and spin-trapping techniques.

Anthraquinones↗

Benzophenone photosensitization of 2'-deoxyguanosine: characterization of the 2R and 2S diastereoisomers of 1-(2-deoxy-beta-D-erythro-pentofuranosyl)- 2-methoxy-4,5-imidazolidinedione. A model system for the investigation of photosensitized formation of DNA-protein crosslinks.

Benzophenone-mediated photosensitization of 2'-deoxyguanosine and its 3',5'-di-O-acetyl derivative, used as DNA model compounds, in oxygen-saturated water-methanol (1:1) solution results in the nucleophilic addition of methanol to the guanine base. The resulting modified nucleosides have been isolated by reverse-phase high-performance liquid chromatography and characterized by extensive spectroscopic measurements including 13C and 1H nuclear magnetic resonance, fast atom bombardment mass spectrometry and circular dichroism as the 2R and 2S diastereoisomers of 1-(2-deoxy-beta-D-erythro-pentofuranosyl)-2-methoxy-4,5-imidazolinedione and their related 3',5'-di-O-acetyl derivates. Information concerning the absolute configuration of the two pairs of diastereoisomers was inferred from detailed nuclear Overhauser effect experiments. A reaction mechanism, involving guanine radical intermediates, is proposed to explain the generation of these new guanine photoproducts.

Benzophenones↗

Photosensitivity.

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Acquired Immunodeficiency Syndrome↗

Molecular mechanism of drug photosensitization: VIII. Effect of inorganic ions on membrane damage photosensitized by naproxen.

The inhibitory effect of Cu2+, Mn2+, Co2+, and I- on naproxen-induced photohemolysis was investigated. In order to better understand this effect, these ions were also tested for lipid peroxidation and protein crosslinking, which are among the main processes involved in erythrocyte membrane damage. The overall results support the hypothesis that metal cations act via a redox scavenging of the radicals which are produced on the lipid component of the membrane. This process occurs through hydrogen abstraction operated by photogenerated naproxen radicals. Moreover, copper can also act as a superoxide anion scavenger: its decay is noxious in photohemolysis, whereas it is not in lipid peroxidation. Metal cations, besides, are not able to scavenge protein crosslinking. On the other hand, iodide is able to reduce both processes because it acts as a heavy atom, favoring intersystem crossing to the unreactive triplet state of the drug, thus reducing naproxen photolysis and, as a consequence, the amount of the damaging species produced. This mechanism was supported by luminescence experiments performed in the absence and in the presence of iodide.

Cations, Divalent↗

UVA photosensitivity in photosensitive bullous disease of chronic renal failure.

3 chronic renal failure patients with bullous skin disease are reported. Only 1 was on maintenance hemodialysis, but all were on frusemide. Porphyrin studies failed to show classical porphyric disease. The 3 patients tested showed low minimal etyrhema doses (MED) to ultraviolet A (UVA) but normal threshold to ultraviolet B (UVB).

Adult↗

Molecular mechanism of drug photosensitization. IX. Effect of inorganic ions on DNA cleavage photosensitized by naproxen.

Photocleavage of DNA induced by naproxen and the correlated protective effect by some inorganic ions have been considered. The presence of a DNA complex is suggested and only associated naproxen seems to be responsible for the cleavage, for which the quantum yield of single strand breaks was calculated. The inorganic ions I-, Mn2+, Co2+ and Cu2+ decrease naproxen-photoinduced DNA cleavage. Iodide acts by a heavy atom mechanism, thus inhibiting naproxen photolysis and decreasing the amount of free radicals responsible for the photocleavage both in aerobic and anaerobic conditions. Metallic ions protect only within a range of concentrations, as for higher amounts damaging processes are observed. The protective efficiency of cations decreases with the increase of free drug concentration in the bulk of the solution, due to their involvement in the scavenging of naproxen radicals generated by photolysis of the free drug. In the presence of EDTA the cations show a better protective action. The most likely hypothesis is an inhibiting effect on the damaging processes via a redox cycle. The different behaviors of copper and of the two other cations can be justified by the influence of redox potentials of free and complexed metals and by the superoxide dismutase-like activity of copper.

Animals↗