Miolo Giorgia, Salvador Alessia, Mazzoli Alessandra, Spalletti Anna, Marzaro Giovanni, Chilin Adriana
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
J Photochem Photobiol B. 2014 Sep 5;138:43-54. doi: 10.1016/j.jphotobiol.2014.05.002. Epub 2014 May 15.
Linear (L) and angular (A) 4',5'-dimethylfuroquinazolines (FQZs) were synthesized and studied as furocoumarin analogs. These molecules proved to be photounstable with a photodegradation extent correlated to UVA light doses. Both compounds did intercalate inside the DNA double helix, but were not able to photobind DNA bases under UVA irradiation. This behavior was further rationalized through docking studies. The photosensitizing effects of these compounds were evaluated on Jurkat tumor cells and NCTC-2544 human keratinocytes, with and without antioxidants, to demonstrate the involvement of a photodynamic mechanism. Indeed, significant amounts of singlet oxygen and superoxide anion were generated in the presence of both compounds, that account for the oxidative damage induced to some isolated biological substrates (DNA, amino acids, proteins and lipids). Photophysical studies by use of a flash photolysis set up showed detectable triplet population and production of singlet reactive oxygen species for linear furoquinazoline, which can be responsible for the oxidation of biological substrates, and therefore can affect the cell proliferation.
合成了线性（L）和角形（A）4',5'-二甲基呋喃喹唑啉（FQZs）并将其作为呋喃香豆素类似物进行研究。这些分子被证明对光不稳定，其光降解程度与UVA光剂量相关。两种化合物都能插入DNA双螺旋内部，但在UVA照射下无法光结合DNA碱基。通过对接研究进一步阐明了这种行为。在有和没有抗氧化剂的情况下，评估了这些化合物对Jurkat肿瘤细胞和NCTC-2544人角质形成细胞的光敏作用，以证明光动力机制的参与。实际上，在两种化合物存在的情况下都会产生大量单线态氧和超氧阴离子，这解释了对一些分离的生物底物（DNA、氨基酸、蛋白质和脂质）造成的氧化损伤。使用闪光光解装置进行的光物理研究表明，线性呋喃喹唑啉存在可检测到的三重态粒子和单线态活性氧的产生，这可能是生物底物氧化的原因，因此会影响细胞增殖。
