Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Kanagawa Institute of Technology, Atsugi, Kanagawa, Japan.
Department of Applied Chemistry, Kanagawa Institute of Technology, Atsugi, Kanagawa, Japan.
Photochem Photobiol. 2019 Nov;95(6):1403-1411. doi: 10.1111/php.13138. Epub 2019 Aug 30.
Photodynamic therapy (PDT) is a widely used medicinal treatment for the cancer therapy that utilizes the combination of a photosensitizer (PS) and light irradiation. In this study, we synthesized two novel C fullerene derivatives, compounds 1 and 2, with a psoralen moiety that can covalently bind to DNA molecules via cross-linking to pyrimidine under photoirradiation. Along with several fullerene derivatives, the biological properties of several novel compounds have been evaluated. Compounds 1 and 2, which have been shown to induce the production of hydroxyl radicals using several ROS detecting reagents, induced DNA strand breaks with relatively weak activities in the in vitro detection system using a supercoiled plasmid. However, the psoralen-bound fullerene with carboxyl groups (2) only showed genotoxicity in the genotoxicity assay system of the umu test. Compound 2 was also seen to have cytotoxic activities in several cancer cell lines at higher doses compared to water-soluble fullerenes.
光动力疗法（PDT）是一种广泛应用于癌症治疗的医学治疗方法，它利用了光敏剂（PS）和光照射的结合。在这项研究中，我们合成了两种新型 C60 fullerene 衍生物，化合物 1 和 2，它们具有补骨脂素部分，可在光照射下通过交联与嘧啶形成共价键，从而与 DNA 分子结合。与几种富勒烯衍生物一起，我们评估了几种新型化合物的生物学特性。化合物 1 和 2 被证明可以使用几种 ROS 检测试剂诱导产生羟基自由基，在使用超螺旋质粒的体外检测系统中，它们具有相对较弱的诱导 DNA 链断裂的活性。然而，带有羧基的补骨脂素结合富勒烯（2）仅在 umu 测试的遗传毒性检测系统中表现出遗传毒性。与水溶性富勒烯相比，化合物 2 在较高剂量下对几种癌细胞系也表现出细胞毒性活性。
