Párraga A, Orozco M, Portugal J
Departamento de Bioquímica y Fisiología, Universidad de Barcelona, Facultad de Química, Spain.
Eur J Biochem. 1992 Sep 1;208(2):227-33. doi: 10.1111/j.1432-1033.1992.tb17177.x.
The ability of elsamicin A, an antitumour antibiotic, to cleave DNA in the presence of ferrous iron and reducing agents, has been analysed using experimental and theoretical approaches. Experimentally, the antibiotic causes DNA breakage in the presence of ferrous ions and a reducing agent. The DNA-cleaving activity appears to be partially blocked by the action of superoxide dismutase and catalase. These results indicate that the elsamicin aglycone moiety (chartarin) can be involved in the production of free radicals. We have performed a broad theoretical study based in the quantum-mechanical framework, which allow us to determine the redox properties of elsamicin that lead to the generation of radical species. Our results clearly show that elsamicin acts as a true catalyst in the production of superoxide radicals. Moreover, it is suggested that the oxidation/reduction mechanism of the aglycone moiety of elsamicin (a lactone), leading to DNA breakage, is different from the mechanism followed by other well-known anti-cancer drugs, whose chromophore is a quinone.
利用实验和理论方法，对一种抗肿瘤抗生素——埃尔斯米星A在亚铁离子和还原剂存在下切割DNA的能力进行了分析。实验表明，该抗生素在亚铁离子和还原剂存在时会导致DNA断裂。超氧化物歧化酶和过氧化氢酶的作用似乎会部分阻断DNA切割活性。这些结果表明，埃尔斯米星苷元部分（查塔林）可能参与了自由基的产生。我们在量子力学框架下进行了广泛的理论研究，这使我们能够确定导致自由基物种产生的埃尔斯米星的氧化还原性质。我们的结果清楚地表明，埃尔斯米星在超氧自由基的产生中起真正的催化剂作用。此外，有人提出，埃尔斯米星（一种内酯）苷元部分导致DNA断裂的氧化/还原机制，与其他已知抗癌药物（其发色团为醌）所遵循的机制不同。
