酞菁基抗癌声敏剂的敏化机理、构效关系和设计合成

项目名称： 酞菁基抗癌声敏剂的敏化机理、构效关系和设计合成

项目编号： No.20872016

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 黄剑东

作者单位： 福州大学

项目金额： 30万元

中文摘要： 声动力治疗是在光动力治疗的基础上发展起来的一种高选择性的肿瘤治疗新方法，由于超声具有深度穿透组织能力，该疗法在深部或大体积肿瘤的治疗上具有诱人前景。敏化剂是声/光动力疗法的关键因素，着眼于克服当前声敏剂的缺陷，推动声敏剂合理设计的起步，本项目选择酞菁骨架为母体结构，结合光敏剂的研究经验和超声空化效应的特点，设计合成了系列酞菁衍生物。进而研究了酞菁衍生物在超声激活下产生活性氧的能力（即声敏化能力），探讨了化合物的组成结构特征（包括中心离子、周环与轴向取代基的类型以及相互协调作用等）与声敏化能力的相关性，并通过比较声动力和光动力的差异，了解超声敏化机制。在此基础上，本项目还研究了具有较高声敏化能力的酞菁衍生物的声动力杀伤癌细胞效应，总结了构效关系，并开展分子设计和结构调控，获得了2个具有自主知识产权的新型高效抗癌声敏剂。本研究结果将在一定程度上促进声动力治疗和酞菁化学生物学的发展，也将有益于药物化学、配位化学、光化学、声化学和生命科学等相关学科的交叉发展。本项目已在Tetrahedron等期刊上发表7篇与本研究相关的论文，并申报国家发明专利1项。

中文关键词： 声动力治疗；酞菁；合成；声敏剂；构效关系

英文摘要： Sonodynamic therapy (SDT) is a promising minimal-invasive approach for the treatment of cancers by the combined action of a sonosensitizer and low energy ultrasound.The development of SDT was built on the photodynamic therapy(PDT). Because ultrasound has a unique feature of penetrating deeply into tissue, SDT exhibits an attractive potential in the treatments of the big-volume and/or deep-seated tumors,when compared with PDT. Both for successful PDT and SDT, the performance of sensitizers plays a crucial role. In this project, in order to develop new sonosensitizers with improved properties, the series of novel phthalocyanines have been designed and prepared by consideration of research experiences on photosensitizers and features of ultrasonic cavitations. The efficiency to generate reactive oxygen species (ROS) under ultrasound has been investigated for these phthalocyanines. Their activities of generating ROS under ultrasound were related to the structure characters of the central ions, peripheral and axial substituents on the phthalocyanine skeleton. The mechanism of sonodynamic effects are therefore understood by compared with that of photodynamic actions.The sonodynamic activities against carcinous cells were also examined for the sonosensitive phthalocyanines. Combined with cellular uptake properties, the structure-activity relationships were analyzed. On the basis, two novel high-efficient sonosensitizers have been reasonably designed and prepared. The above studies would promote the development of SDT and chemical biology of phthalocynaines,to a centain degree. These results also can enrich the contents of relative subjects indcuding medicinal chemistry, coordination chemistry, photochemistry, sonochemistry and life sicence. Part results of this study have been published in Tetrahedron and so on journals, and the applications of an inventive patent has also been accepted.

英文关键词： Sonodynamic therapy; Phthalocyanine; Synthesis; Sonosensitizer; Structure-activity Relationship