Vedaldi D, Frank S, Pozzan A, Miolo G, Dall'Acqua F, Caffieri S, Rodighiero P, Guiotto A
Department of Pharmaceutical Sciences, University of Padova, Italy.
Farmaco. 1994 Oct;49(10):615-23.
Pyrroloquinolinones, furocoumarin analogues, contain a divinilbenzene moiety, suggesting possible photoreactivity. Quantum mechanics calculations indicate that the pyrrole-side double bond exhibits strong photoreactivity, while the pyridone-side double bond is only poorly photoreactive. Intercalation models obtained by molecular mechanics calculations suggest that, in the cis-syn intercalation arrangement, the pyridone-side double bond is well aligned with the nearby thymine, supporting possible C4-cycloaddition with the 5,6 double bond of thymine, while the pyrrole-side double bond assumes an unfavourable position for photobinding. These data suggest that photoreaction between the pyridone-side and thymine double bonds may takes place, although with very low yield. Experimental evidence concerning DNA-photobinding exhibited by 2,6-dimethyl-9-methoxy-4H-pyrroloquinolinone (Compound I) confirms theoretical predictions. The formation of C4-cycloadducts between the pyridone side double bond and thymine also takes place with very low yield. Compound I shows marked BSA photobinding, suggesting that pyrroloquinolinones may photoreact with proteins. The three pyrroloquinolinones examined show high yields of singlet oxygen generation, suggesting that photobiological effects may be obtained through this photodynamic pathway, rather than through DNA photobinding.
吡咯并喹啉酮类，即呋喃香豆素类似物，含有二乙烯基苯部分，表明可能具有光反应性。量子力学计算表明，吡咯侧双键表现出很强的光反应性，而吡啶酮侧双键的光反应性则很差。通过分子力学计算得到的嵌入模型表明，在顺式-顺式嵌入排列中，吡啶酮侧双键与附近的胸腺嘧啶排列良好，支持与胸腺嘧啶的5,6双键可能发生C4环加成，而吡咯侧双键在光结合时处于不利位置。这些数据表明，吡啶酮侧双键与胸腺嘧啶双键之间可能发生光反应，尽管产率很低。关于2,6-二甲基-9-甲氧基-4H-吡咯并喹啉酮（化合物I）表现出的DNA光结合的实验证据证实了理论预测。吡啶酮侧双键与胸腺嘧啶之间形成C4环加合物的产率也很低。化合物I表现出明显的牛血清白蛋白光结合，表明吡咯并喹啉酮类可能与蛋白质发生光反应。所研究的三种吡咯并喹啉酮类显示出高产率的单线态氧生成，表明光生物学效应可能通过这种光动力途径获得，而不是通过DNA光结合。
