Phototoxic metabolites

This phototoxic metabolite was isolated first from the fungus Fusicoccurn amygdali Del Recently it has been isolated from different Semecarpus species... 

Phytoalexins and Phototoxins in Plant Pest Control presents a model approach to the binding of a phytoalexin elicator to DNA, studies of phytoalexins in cotton and peanuts, chapters on phototoxic metabolites of tropical plants and on photosensitizing porphyrins as herbicides. 

Plants are capable of producing a seemingly limitless number of compounds, many of which have proven to be toxic to one or more types of organisms. Phototoxic metabolites are more limited in their distribution, but have a broad spectrum of biocidal activity and appear to provide their hosts with formidable chemical defenses against potential invaders. Certain plant families such as the Rutaceae, Asteraceae, and Apiaceae are well known for their phototoxic abilities while this characteristic is less conunon in others. 

Li and Chignell examined the photochemistry of chlorpromazine and its metabolites 7-hydroxychlorpromazine, demethylchlorpromazine, dideme-thylchlorpromazine and chlorpromazine sulphoxide. They found that all of the compounds except the sulphoxide underwent photodechlorination which was more rapid in the absence of air. It was concluded that the yield of dechlorinated product was directly related to the degree of phototoxicity [209]. 

Not only does chlordiazepoxide (388) show phototoxicity, but so do two of its metabolites, demethylchlordiazepoxide and demoxepam (389). The first of these is formed by /V-demethylation of the drug and this is followed by oxidative deamination to give demoxepam. Both derivatives therefore retain the IV-oxide group, which proved to be the seat of the phototoxicity. When irradiated in isopropanol at 350 nm for a few minutes, all three compounds gave oxaziridines [10, 225],... 

Phototoxicity of Plant Secondary Metabolites to Mosquito Larvae... 

Phototoxicity is photosensitivity that is independent of immunological responses. Phototoxic responses are dose dependent and will affect almost anyone when sufficient dosage is applied or when taken concurrent with UV exposure. In phototoxic reactions, photoactivated chemicals cause direct cellular damage. UV absorption produces either excited state chemicals or metabolites of these chemicals. These, in turn, can be converted into either free radicals or singlet oxygen, either of which results in biomo-lecular oxidation)10 ... 

Wagai, N and Tawara, K. Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice. Arch. Toxicol., 65, 495-499, 1991. 

Santella et al. (1994) also observed urinary excretion of PAH metabolites after dermal application of coal tar, indicating absorption. Studies confirming that coal tar creosote is capable of inducing phototoxicity of the skin indicate dermal absorption after exposure (Diette et al. 1983). 

Ljunggren, B. and Moller, H. (1977) Phenothiazine phototoxicity an experimental study on chlorpromazine and its metabolites, J. Invest. Dermatol., 68 313-317. 

The phototoxic effects of chlorpromazine may be partly due to its metabolites (see references in Harber et al., 1982). Photodynamic and nonphotodynamic processes have been demonstrated for this drug. Stable photoproducts of the drug may account for some of its effects. The action spectrum for chlorpromazine phototoxicity is red-shifted (max at 330 nm) compared with its absorption spectrum (max at 305 nm). This may be due to the shape of the penetration spectrum of light into tissue and/or... 

Adverse effects may also occur as a consequence of the formation of toxic or photoreactive degradation products. For instance, when photolysis of the drug molecule occurs on or near the epidermal layer, lipophilic degradation products would be expected to partition into cell membranes and be cleared only slowly from the system. If the chromophore is retained, the generation of phototoxic species (e.g., free radicals, ROS) may be observed even when the parent compound is fully degraded. For many compounds, it is found that phototoxic degradation products may be formed by photodecomposition of the parent compound or by metabolic pathways. Isolation and identification of degradation products combined with photoreactivity studies of these compounds and of known metabolites are therefore important (Kristensen et al., 1997). 

Pharmacokinetic aspects must be taken into account in cases in which the in vitro screening indicates that the compound is likely to cause phototoxic reactions in vivo. This includes information about in vivo metabolites and degradation products (if available). Phototoxicity is generally dose dependent, i.e., dependent on the concentration of the drug sensitizer and the intensity of the incident radiation at the site of action. Prior to a phototoxic reaction, the sensitizer must be distributed to tissues that are exposed to irradiation and further absorb the light that penetrates these tissues. If no pharmacokinetic data are available, the probability of being retained in a lipophilic medium can be predicted to some extent from the pKa and/or the log P value of the compound. 

Bosca, F., Canudas, N., Marin, M.L., and Miranda, M.A. (2002) A photophysical and photochemical study of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal antiinflammatory drug nabumetone, Photochem. Photobiol., 71, 173-177. 

Over 400 species of tropical plants from 76 families were assayed for phototoxic activity. Furanocoumarins, an important class of phototoxins, were identified from three genera of the Moraceae (fig family). Dorstenia. an herbaceous member of this family, was particularly rich in these metabolites. The distribution of furanocoumarins in the Moraceae as well as evolutionary and ecological aspects are discussed. 

The exact mechanisms of voriconazole-associated photosensitivity are unknown, but inhibition of retinoid metabolism or a direct phototoxic effect of voriconazole or its N-oxide main metabolite, formed by the action of CYP2C19, has been implicated. There was no significant correlation between the incidence of photosensitivity and voriconazole serum concentrations in six children with allergic bronchopulmonary aspergillosis [3T]. In a retrospective study of 24 lung transplant recipients with cystic fibrosis who took voriconazole, heterozygous carriers of the CYP2C19 2 allele required lower maintenance doses than... 

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