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. In phosphate buffer, approximately 80% of fluocinolone acetonide decomposes after 5 J/cm2 of UV-B irradiation, whereas under 30 J/cm2 of UV-A light approximately only 20% decomposes. Both the drug and its photoproducts have been evaluated through a battery of in vitro studies and found to cause photohemolysis and induce photodamage to proteins (erythrocyte ghosts, bovine serum albumin) and linoleic acid. In addition, one of the photoproducts (the 17-hydroperoxy derivative) is highly toxic in the dark. Therefore, both loss of therapeutic activity and light-induced adverse effects may be expected when patients expose themselves to sunlight after drug administration. A major mechanism for phototoxicity involves radicals forming from drug breakdown, at least under UV-B, although reactive oxygen species may play a role, particularly under UV-A.     

Photochemistry and phototoxicity studies of flutamide, a phototoxic anti-cancer drug

The phototoxic anti-cancer drug flutamide is photolabile under UV-B light in either aerobic or anaerobic conditions. Irradiation of a methanol solution of this drug produces several photoproducts, one by photoreduction of the nitro group, one by rupture of the aromatic-NO2 bond of the parent compound, two as a result of the rupture of the CO-NH bond and one derived from the photoreduction product by scission of the aromatic-NH2 bond. Flutamide shows a photohemolytic effect on human erythrocytes and photoinduces lipid peroxidation. Studies on peripheral blood polymorphonuclear cells (neutrophils) demonstrated the phototoxicity of flutamide as well as inhibition of the cytotoxicity respiratory burst by the photoproduct derived from its photoreduction. The results suggest that the inhibition of the respiratory burst observed in phorbol myristate acetate (PMA)-activated cells is mediated by photosensitization and concomitant singlet oxygen production and/or formation of toxic photoproducts.     

高效液相色谱法快速测定大黄中大黄素,大黄酸和芦荟大黄素的研究

研究了高效液相色谱法测定大黄中大黄素、大黄酸和芦荟大黄素。大黄中大黄素、大黄酸和芦荟大黄素用氯仿加热回流提取,提取液蒸干溶剂,以甲醇溶解定容待测。以安捷仑ZORBAX Stable Bound(4.6 mm×50 mm,1.8μm)色谱柱为固定相,质量分数0.1%的H3PO4和甲醇为流动相,梯度洗脱(0 min:VH3PO4∶V甲醇=27∶73;1 min:100%甲醇);在该色谱条件下,大黄素、大黄酸和芦荟大黄素在2.0 min内可达到基线分离;用紫外二极管矩阵检测器检测。方法标准回收率为99.4%~102%,相对标准偏差为1.5%~1.8%。可用于大黄中大黄素、大黄酸和芦荟大黄素的快速分析检测。     

Simultaneous determination and pharmacokinetic studies of aloe emodin and chrysophanol in rats after oral administration of Da-Cheng-Qi decoction by high-performance liquid chromatography

A validated high-performance liquid chromatography (HPLC) method was developed for simultaneous determination and pharmacokinetic study of aloe emodin and chrysophanol in rats. It was performed on a reverse-phase C(18) column and a mobile phase made up of methanol and 0.2% acetic acid (83:17, v/v). The ultraviolet detection was 254 nm. 1,8-dihydroxyanthraquinone was used as the internal standard. The assay was linear over the range 28-2800 ng/mL (r(2) = 0.9993) for aloe emodin and 25.6-2560 ng/mL (r(2) = 0.9991) for chrysophanol. The average percentage recoveries of three spiked plasmas were 98.8-104.8% and 97.7-103.2% for aloe emodin and chrysophanol, respectively. Their RSD of intra-day and inter-day precision at concentrations of 56, 280 and 1400 ng/mL for aloe emodin and 51.6, 258 and 1290 ng/mL for chrysophanol were less than 3.5%. This method was applied for the first time to simultaneously determinate aloe emodin and chrysophanol in rats following oral administration of traditional Chinese medicine of Da-Cheng-Qi decoction. The pharmacokinetic parameters showed that chrysophanol was better absorbed with higher concentrations in plasma than aloe emodin did. They both eliminated slowly in male rats. The assay is suitable for identifying the plasma and tissue levels of aloe emodin and chrysophanol in preclinical investigations.     

Induction of primary cutaneous melanomas in C3H mice by combined treatment with ultraviolet radiation, ethanol and aloe emodin

The role of ultraviolet (UV) radiation in the induction of nonmelanoma skin cancer is widely accepted, although its precise contribution to the development of primary cutaneous melanoma skin cancer requires further definition. We found that painting aloe emodin, a trihydroxyanthraquinone from Aloe barbadensis, in ethyl alcohol vehicle on the skin of mice in conjunction with exposure to UVB (280-320 nm) radiation results in the development of melanin-containing skin tumors. C3H/HeN mice were treated thrice weekly with aloe emodin in a 25% ethanol in water vehicle and exposed to 15 kJ/m2 UV radiation. Neither ethanol vehicle nor aloe emodin alone induced skin tumors in the absence of UV radiation. In two separate experiments, 20-30% of the mice treated with a combination of UV radiation and ethanol vehicle and 50-67% of the UV-irradiated animals given aloe emodin in ethanol vehicle developed primary cutaneous melanin-containing tumors. The diagnosis of melanoma was established using Fontana silver stain for melanin; these tumors were negative for vimentin and keratin. Melanin-containing melanosomes were observed by transmission electron microscopy in tumors diagnosed as melanomas. Although the mechanism of carcinogenesis in these mice is currently unknown, our findings have led to the development of the first facile murine model for the induction of primary melanoma. This model has the potential to clarify the role of UV radiation in the etiology of malignant melanoma.     

Metalloporphyrin phototoxicity

The phototoxicities of six metalloporphyrin dimethylesters (i.e. cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), tin (Sn) and zinc (Zn) were investigated. Hemolysis of human erythrocytes and inactivation of two enzymes (acetylcholinesterase and beta-galactosidase) were used to assess the phototoxic efficacy of these metal chelates. Tin protoporphyrin (SnPP), the only porphyrin found to hemolyze erythrocytes at a concentration of 40 microM (radiation dose, 230 kJ m-2), was much less efficient than either free protoporphyrin IX or hematoporphyrin. SnPP completely inactivated beta-galactosidase at concentrations above 15 microM (radiation dose, 75 kJ m-2) and drastically interfered with acetylcholinesterase activity at a concentration of 150 microM (radiation dose, 75 kJ m-2). CoPP, CuPP, MnPP, NiPP and ZnPP were ineffective photohemolytic agents at 40 microM (radiation dose, 230 kJ m-2), but inactivated acetylcholinesterase and beta-galactosidase activity to varying degrees. These results suggest that (i) metal ions reduce the phototoxicity of protoporphyrin IX, (ii) different metal ions reduce the phototoxic activity of protoporphyrin IX to different degrees and (iii) the biological activities of the various metal complexes vary in different assay systems.     

Ocular phototoxicity.

The human eye is constantly exposed to sunlight and artificial lighting. Therefore the eye is exposed to UV-B (295-320 nm), UV-A (320-400 nm), and visible light (400-700 nm). Light is transmitted through the eye and then signals the brain directing both sight and circadian rhythm. Therefore light absorbed by the eye must be benign. Damage to the young and adult eye by intense ambient light is avoided because the eye is protected by a very efficient antioxidant system. In addition, there are protective pigments such as the kynurenines, located in the human lens, and melanin, in the uvea and retina, which absorb ambient radiation and dissipate its energy without causing damage. After middle age there is a decrease in the production of antioxidants and antioxidant enzymes. At the same time, the protective pigments are chemically modified (lenticular 3-hydroxy kynurenine pigment is enzymatically converted into the phototoxic chromophore xanthurenic acid; melanin is altered from an antioxidant to pro-oxidant) and fluorescent chromophores (lipofuscin) accumulate to concentrations high enough to produce reactive oxygen species. We have known for some time that exposure to intense artificial light and sunlight either causes or exacerbates age-related ocular diseases. We now know many of the reasons for these effects, and with this knowledge methods are being developed to interfere with these damaging processes.     

Phosphorylation of emodin

A convenient method has been developed for the interaction of dialkyl phosphites with 1,6,8-trihydroxy-3-methylanthraquinone (emodin) under the conditions of the Todd—Atherton reaction. It has been shown that the α-hydroxy groups of emodin are not phosphorylated at an equimolar ratio of emodin and dialkyl phosphite. The phosphorylation of 7-bromo-1,6,8-trihydroxy-3-methylanthraquinone with potassium dialkyl phosphorothioates has been studied. The reaction takes place at the sulfur atom, with the formation of of the product of S-alkylation.     

Phosphorylation of emodin

A convenient method has been developed for the interaction of dialkyl phosphites with 1,6,8-trihydroxy-3-methylanthraquinone (emodin) under the conditions of the Todd—Atherton reaction. It has been shown that the -hydroxy groups of emodin are not phosphorylated at an equimolar ratio of emodin and dialkyl phosphite. The phosphorylation of 7-bromo-1,6,8-trihydroxy-3-methylanthraquinone with potassium dialkyl phosphorothioates has been studied. The reaction takes place at the sulfur atom, with the formation of of the product of S-alkylation.Al-Farabi Kazakh State National University, Almaty. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 212–216, March–April, 1994.     

Bromination of emodin

Using emodin as an example, it has been shown that in the bromination of hydroxyanthraquinones the qualitative composition and quantitative ratio of the reaction products depend on the nature of the brominating agent and the solvent, the ratio of the rea Lants, and the temperature regime. In order to obtain bromo-3-methyl-1,6,8-trihydroxyanthraquinone it is recommended to use dioxane dibromide in acid solution as the brominating agent, and to obtain 5-bromo-3-methyl-1,6,8-trihydroxyanthraquinone the same reagent in dioxane solution. The optimum conditions for obtaining 3-bromomethyl-1,6,8-trihydroxyanthraquinone by the methods of initiated bromination and photobromination have been selected. S. M. Kirov Kazakh State University, Alma-Ata. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 618–621, September–October, 1990.     

Bromination of emodin

Using emodin as an example, it has been shown that in the bromination of hydroxyanthraquinones the qualitative composition and quantitative ratio of the reaction products depend on the nature of the brominating agent and the solvent, the ratio of the rea Lants, and the temperature regime. In order to obtain bromo-3-methyl-1,6,8-trihydroxyanthraquinone it is recommended to use dioxane dibromide in acid solution as the brominating agent, and to obtain 5-bromo-3-methyl-1,6,8-trihydroxyanthraquinone the same reagent in dioxane solution. The optimum conditions for obtaining 3-bromomethyl-1,6,8-trihydroxyanthraquinone by the methods of initiated bromination and photobromination have been selected.S. M. Kirov Kazakh State University, Alma-Ata. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 618–621, September–October, 1990.     

影像科学与光化学(原名 感光科学与光化学)

<正>本刊主要刊登影像科学和光化学领域的研究成果,同时刊登有关信息科学及信息材料,包括信息储存和记录、信息的处理和加工及信息显示材料等;光/电化学及光电子技术,包括光/电转换及储存材料、电光材料、非线性光学材料、纳米材料、电致发光材料及器件研究以及化学和物理发光等领域;光生物,光医学及生命科学与环境科学中的有关问题的新理论、新概念、新技术和新方法.     

影像科学与光化学(原名感光科学与光化学)

<正>本刊主要刊登影像科学和光化学领域的研究成果,同时刊登有关信息科学及信息材料,包括信息储存和记录、信息的处理和加工及信息显示材料等;光/电化学及光电子技术,包括光/电转换及储存材料、电光材料、非线性光学材料、纳米材料、电致发光材料及器件研究以及化学和物理发光等领域;光生物,     

Theoretical study of ibuprofen phototoxicity

The photochemical properties and degradation of the common nonsteroid anti-inflammatory drug ibuprofen is studied by means of hybrid density functional theory. Computed energies and properties of various species show that the deprotonated form dominates at physiological pH, and that the species will not be able to decarboxylate from a singlet excited state. Instead, decarboxylation will occur, with very high efficiency, provided the deprotonated compound can undergo intersystem crossing from an excited singlet to its excited triplet state. In the triplet state, the C-C bond connecting the carboxyl group is elongated, and the CO2 moiety detaches with a free energy barrier of less than 0.5 kcal/mol. Depending on the local environment, the decarboxylated product can then either be quenched through intersystem crossing (involving the possible formation of singlet oxygen) and protonation, or serve as an efficient source for superoxide anions and the formation of a peroxyl radical that will initiate lipid peroxidation.     

影像科学与光化学(原名感光科学与光化学)

<正>本刊主要刊登影像科学和光化学领域的研究成果,同时刊登有关信息科学及信息材料,包括信息储存和记录、信息的处理和加工及信息显示材料等;光/电化学及光电子技术,包括光/电转换及储存材料、电光材料、非线性光学材料、纳米材料、电致发光材料及器件研究以及化学和物理发光等领域;光生物,光医学及生命科学与环境科学中的有关问题的新理论、新概念、新技术和新方法,以促进国内外的学术交流.     

计算光化学

本文从光化学的最基本概念入手,简要介绍了计算光化学理论方法的发展历程和典型应用,并对不同时期的工作做简要评述,以期读者对整个计算光化学有一个整体的了解。本文还介绍了计算机硬件的发展对计算光化学的影响。最后指出目前计算光化学研究的困难和存在问题以供同行讨论。     

影像科学与光化学

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Photochemistry and photophysics of thienocarbazoles

Two methylated thienocarbazoles and two of their synthetic nitro-precursors have been examined by absorption, luminescence, laser flash photolysis and photoacoustic techniques. Their spectroscopic and photophysical characterization involves fluorescence spectra, fluorescence quantum yields and lifetimes, and phosphorescence spectra and phosphorescence lifetimes for all the compounds. Triplet-singlet difference absorption spectra, triplet molar absorption coefficients, triplet lifetimes, intersystem crossing S1 --> T1 and singlet molecular oxygen yields were obtained for the thienocarbazoles. In the case of the thienocarbazoles it was found that the lowest-lying singlet and triplet excited states, S1 and T1, are of pi,pi* origin, whereas for their precursors S1 is n,pi*, and T1 is pi,pi*. In both thienocarbazoles it appears that the thianaphthene ring dictates the S1 --> T1 yield, albeit there is less predominance of that ring in the triplet state of the linear thienocarbazole, which leads to a decrease in the observed phiT value.