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光毒性非甾体抗炎镇痛药萘丁美酮的主要代谢产物6-甲氧基-2-萘乙酸的光敏特性。

Photosensitizing properties of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal anti-inflammatory and analgesic drug nabumetone.

作者信息

Canudas N, Zamora D, Villamizar J E, Fuentes J, Castelli C, Taddei A

机构信息

Laboratorio de Fotoquímica y Fotobiología, Departamento de Química, Universidad Simón Bolívar, Venezuela.

出版信息

Pharmazie. 2005 Aug;60(8):604-8.

PMID:16124404
Abstract

The photobiological properties of 6-methoxy-2-naphthylacetic acid (6-MNAA) were studied using a variety of in vitro phototoxicity assays: photohemolysis, photoperoxidation of linoleic acid, photosensitized degradation of histidine and thymine and the Candida phototoxicity test. 6-MNAA was phototoxic in vitro. 6-MNAA reduced nitro blue tetrazolium (NBT) when irradiated with lambda > or = 300 nm in deoxygenated aqueous buffer solution (pH 7.4). NBT can be reduced by reaction with the excited state of 6-MNAA subject to interference with molecular oxygen. The photohemolysis rate was inhibited by the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO), sodium azide (NaN3) and reduced glutathione (GSH). Photoperoxidation of linoleic acid and photosensitized degradation of histidine and thymine were significantly inhibited by sodium azide and reduced glutathione. 6-MNAA was phototoxic to C. albicans, C. lipolytica and C. tropicalis. A mechanism involving singlet oxygen, radicals, and electron transfer reactions is suggested for the observed phototoxicity.

摘要

使用多种体外光毒性试验研究了6-甲氧基-2-萘乙酸(6-MNAA)的光生物学特性:光溶血、亚油酸的光过氧化、组氨酸和胸腺嘧啶的光致敏降解以及念珠菌光毒性试验。6-MNAA在体外具有光毒性。在脱氧缓冲水溶液(pH 7.4)中,当用波长大于或等于300 nm的光照射时,6-MNAA可使硝基蓝四唑(NBT)还原。NBT可通过与6-MNAA的激发态反应而还原,但会受到分子氧的干扰。1,4-二氮杂双环[2.2.2]辛烷(DABCO)、叠氮化钠(NaN₃)和还原型谷胱甘肽(GSH)的存在可抑制光溶血速率。叠氮化钠和还原型谷胱甘肽可显著抑制亚油酸的光过氧化以及组氨酸和胸腺嘧啶的光致敏降解。6-MNAA对白色念珠菌、解脂念珠菌和热带念珠菌具有光毒性。对于观察到的光毒性,提出了一种涉及单线态氧、自由基和电子转移反应的机制。

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Photosensitizing properties of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal anti-inflammatory and analgesic drug nabumetone.光毒性非甾体抗炎镇痛药萘丁美酮的主要代谢产物6-甲氧基-2-萘乙酸的光敏特性。
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