氯尼达明[1-(2,4-二氯苄基)-1H-吲唑-3-羧酸]的光化学和光毒性特性研究。

Study of the photochemical and phototoxic properties of lonidamine [1-(2,4-dichlorobenzyl)-1H-indazol-3-carboxylic acid].

作者信息

Chekulayev V, Shevchuk I, Chekulayeva L, Kahru A

机构信息

Institute of Chemistry, Department of Bioorganic Chemistry, Tallinn, Estonia.

出版信息

J Photochem Photobiol B. 1997 Nov;41(1-2):11-21. doi: 10.1016/s1011-1344(97)00062-6.

DOI:10.1016/s1011-1344(97)00062-6

PMID:9440309

Abstract

Lonidamine (LND) is an antispermatogenic and antitumour agent acting via inhibition of the energy metabolism. According to our results LND in vitro acted as a photosensitizer enhancing synergistically the lethal action of UV radiation (lambda max = 330 nm, the range between 260-390 nm) towards Ehrlich carcinoma cells (EAC). The primary targets of phototoxic action of LND probably were cell membranes and mitochondria. UV irradiation of EAC in the presence of LND increased the permeability of the plasma membranes, stimulated the photoperoxidation of lipids, enhanced the inhibition of dehydrogenase activity and oxygen consumption of the cells. Deficiency of oxygen substantially decreased phototoxicity of LND. LND may induce photosensitized destruction of biomolecules by acting through type 1 and 2 reactions. It could be supposed that negative side effects of LND (e.g., photophobia and photosensitivity that have been reported for some cancer patients treated with LND) could be associated with its photosensitizing properties.

摘要

氯尼达明（LND）是一种通过抑制能量代谢发挥作用的抗生精和抗肿瘤药物。根据我们的研究结果，LND在体外作为一种光敏剂，能协同增强紫外线辐射（最大波长=330nm，波长范围在260-390nm之间）对艾氏腹水癌细胞（EAC）的致死作用。LND光毒性作用的主要靶点可能是细胞膜和线粒体。在LND存在的情况下对EAC进行紫外线照射，会增加质膜的通透性，刺激脂质的光过氧化，增强对细胞脱氢酶活性和氧消耗的抑制。缺氧会显著降低LND的光毒性。LND可能通过1型和2型反应诱导生物分子的光敏性破坏。可以推测，LND的负面副作用（例如，据报道一些接受LND治疗的癌症患者出现的畏光和光敏反应）可能与其光敏特性有关。