The photodegradation of quercetin: relation to oxidation.

The photostability of quercetin in alcoholic solutions was studied. Both UVA and UVB light induced degradation of quercetin, yielding a single product 1 deriving from oxidation and addition of an alcohol molecule to the 2,3 double bond. The same mechanism operated when quercetin was dissolved in alkaline solutions, and again a product 2 due to oxidation and addition of water was characterized.

A novel tetrahydrobenzoangelicin with dark and photo biological activity.

The synthesis of 8,9,10,11-tetrahydro-5-(3-dimethylaminopropoxy)-4-methylbenzofuro[2,3-h]coumarin (5) is described. The new compound showed the ability to inhibit cell growth both upon UVA irradiation and in the dark. The investigation on the mechanism of action highlighted the capacity of 5 to covalently photoadd to thymine, as demonstrated by the isolation and characterization of the 4',5'-monoadduct.

Photoreactivity of 5-fluorouracil under UVB light: photolysis and cytotoxicity studies.

The photodegradation of the chemotherapeutic agent 5-fluorouracil (5-FU) under UVB light was studied both in aqueous and methanol solutions and in systemic and topical formulations. As monitored by HPLC, photodegradation in solution takes place in a concentration dependent manner; thus, the solution for parenteral administration (10(-1) M) showed negligible loss of the active principle. On the contrary, the commercial cream containing 5% of 5-FU showed low stability under UVB exposure.

Erythroid induction of chronic myelogenous leukemia K562 cells following treatment with a photoproduct derived from the UV-A irradiation of 5-methoxypsoralen.

Induction of terminal erythroid differentiation can be an efficient strategy to inhibit proliferation of chronic myelogenous leukemia cells. Psoralens, well-known photo-chemotherapeutic agents, were found to be efficient at inducing erythroid differentiation of K562 cells, an in vitro cell line isolated from the pleural effusion of a patient with chronic myelogenous leukemia in blast crisis. The effects of crude pre-irradiated solutions of 5-methoxypsoralen on erythroid differentiation of human leukemic K-562 cells were evaluated.

UVB photolysis of betamethasone and its esters: characterization of photoproducts in solution, in pig skin and in drug formulations.

The stability of the synthetic glucocorticosteroid betamethasone under UVB light was studied both in vitro (water and methanol solution and in topical and injectable commercial formulations) and ex vivo (pig skin). From irradiated methanol solutions three main photoproducts were isolated by HPLC and TLC and characterized by NMR/MS analyses. The modifications involve parts of the molecule peculiar for the therapeutic activity, that is, rearrangement of ring A ("lumi"- and "photolumiderivatives"), and Norrish Type I fragmentation of the ketolic chain ("androderivative").

UVB photolysis of hydrocortisone 21-acetate.

Hydrocortisone 21-acetate (HCA) in methanol solution undergoes photodegradation under UVB light, as monitored by HPLC. Five main photoproducts have been isolated and characterized by means of NMR and mass spectroscopy. One of them derives from a Norrish I photoreaction which cleaves the C17-C20 bond of the steroid yielding the andro-derivative, a second product comes from a Yang-type photorearrangement which links C18 to C20 yielding a cyclobutane adduct.

Photoaddition of fluphenazine to nucleophiles in peptides and proteins. Possible cause of immune side effects.

By the action of UVA light, fluphenazine reacted with nucleophiles through a mechanism involving defluorination of its trifluoromethyl group, giving rise to carboxylic acid derivatives that were easily detected by electrospray mass spectrometry. This photoreaction took place with alcohols, sulphydryls, and amines. When irradiation of fluphenazine was carried out in the presence of an amino acid at pH 7.

The mitochondrial effects of novel apoptogenic molecules generated by psoralen photolysis as a crucial mechanism in PUVA therapy.

The generation of photoproducts of psoralen (POPs) might be relevant in cell death induced by psoralen plus UVA, namely PUVA, which is a recognized effective treatment for cutaneous T-cell lymphoma, chronic graft-versus-host disease, and psoriasis. We investigated the occurrence of POP-induced cell death and the underlying mechanisms. POPs were produced by irradiating a psoralen solution with UVA.

Mechanism of action of 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one, a very active angular furocoumarin-like sensitizer.

The molecular structure of 1,4,6,8-tetramethylfuro[2,3-h]quinolin-2(1H)-one (FQ), a recent furocoumarin-like photosensitizer, has been modified with the aim of reducing its strong genotoxicity, by replacing the methyl group at 4 position with a hydroxymethyl one, and so obtaining 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ). This modification gave rise to a strong reduction of lipophilicity and dark interaction with DNA. The formation of monoadducts (MA) was deeply affected, whereas the induction of bifunctional adducts between DNA and proteins (DPC(L>0)) was replaced by an efficient production of DNA-protein cross-links at zero length (DPC(L=0)), probably via guanine damage.

Mitochondria and plasma membrane as targets of UVA-induced toxicity of neuroleptic drugs fluphenazine, perphenazine and thioridazine.

In order to gain insights into the mechanism of phototoxicity of the neuroleptic drugs fluphenazine, perphenazine and thioridazine in cultured cells, studies were performed with murine 3T3 fibroblasts, aimed at identifying some cellular targets responsible for photoinduced cell death and possible cytotoxic reactive species involved in the photosensitization process. 3T3 fibroblasts incubated with 5 microM drugs and irradiated with UVA light (up to 8 J/cm2) underwent cell death, the extent of which depended on light dose. Of the three drugs, fluphenazine exhibited the highest phototoxicity and 100% cell death was achieved with a light dose of 5 J/cm2.

Photochemistry and phototoxicity of fluocinolone 16,17-acetonide.

Fluocinolone 16,17-acetonide is a corticosteroid used topically to treat various inflammatory skin diseases. Its photoreactivity was studied under UV-A and UV-B light in aqueous buffer in the presence of oxygen. This drug is photolabile under UV-B light and, to a lesser extent, under UV-A light, which is absorbed far less.

1-Thioangelicin: crystal structure, computer-aided studies and photobiological activity.

1-Thioangelicin is a furocoumarin analog synthesized to investigate the role of the substitution of sulfur for oxygen in the parent compound angelicin. The compound was examined by X-ray diffraction, and its interaction with DNA, both in the dark and by UVA irradiation, studied by means of linear flow dichroism, chromatography and (1)H NMR. Further insight into the steric and electronic features of 1-thioangelicin has been reached through theoretical calculations, including molecular mechanics optimization, docking studies and frontier molecular orbital investigations.

In vitro phototoxic properties of triamcinolone 16,17-acetonide and its main photoproducts.

The phototoxicity of triamcinolone 16,17-acetonide has been estimated through a panel of in vitro tests. The main target involved in phototoxicity induced by triamcinolone appeared to be the cell membrane. Oxygen-independent photohemolysis was observed.

Topically applied vitamin C and cysteine derivatives protect against UVA-induced photodegradation of suprofen in ex vivo pigskin.

Exposure of the nonsteroidal anti-inflammatory drug suprofen (SUP) to UV-radiation results in the formation of radicals, reactive oxygen species (ROS), photodecarboxylated products and photoadducts with biomacromolecules. Using an ex vivo pigskin explant model, we investigated whether topical coapplication of the water-soluble antioxidants vitamin C (Lascorbic acid, ASC), N-acetyl-L-cysteine (NAC) or L-cysteine ethylester (CYSET) with SUP reduced ultraviolet A (UVA)-induced decomposition of SUP. UVA-induced changes in antioxidant bioavailability in the stratum corneum and epidermis were also studied.

Furocoumarin photolysis: chemical and biological aspects.

Furocoumarins (psoralens) undergo photolysis when subjected to UVA radiation in solution. Several products are formed, depending on the molecular structure and experimental conditions. Some products are the result of anoxic mechanisms (cyclodimerisation, addition of solvent), others of oxic pathways, leading to oxidised products.

Photoisomerization of fluvoxamine generates an isomer that has reduced activity on the 5-hydroxytryptamine transporter and does not affect cell proliferation.

Fluvoxamine, a selective serotonin re-uptake inhibitor, is used as antidepressant/anxiolytic. The presence of a C=N double bond in the structure of fluvoxamine implies the existence of two geometric isomers: E- (trans) and Z- (cis), and suggests the hypothetical susceptibility of the molecule to photoisomerization. Clinically effective fluvoxamine is in its trans form.

PUVA-induced apoptosis involves mitochondrial dysfunction caused by the opening of the permeability transition pore.

The mechanism of cell death was investigated in Jurkat cells exposed to the combination of psoralen and UVA irradiation (PUVA). Apoptosis was by far prevailing over necrosis and involved mitochondrial dysfunction. The collapse of mitochondrial membrane potential, appears to be caused by the opening of the mitochondrial permeability transition pore since its inhibitor, cyclosporin A, prevented mitochondrial dysfunction and largely attenuated apoptosis.

Photobiological properties of hydroxy-substituted flavothiones.

Flavothione (FT) and a series of 18 hydroxy- and methoxy-substituted flavothiones were screened for photobiological activity. The 5-hydroxy-substituted compounds (group 3) and the methoxy-substituted flavothiones were inactive. FT and the remaining hydroxy-substituted compounds, all displayed photobiological activity.