氮氧自由基标记苷类及酚类天然产物衍生物的合成及其抗辐射性能研究

Modern biology and medical research has shown that ionizing radiation is an important factor to cause cell damage, the body dysfunction and even death.Currently, radiotherapy is an effective means of treating cancer, has widespread clinical application. The existing drugs for clinical radiation protection is scarce, only thiamine compounds, hormones, cytokines and few categories. However, it has been limited in clinical due to the strong side effects. Current research has shown that natural pharmaceutically active ingredient has a wide source of readily available, low toxicity, good biocompatibility and other advantages, the development of radiation protection drug has become a research hotspot.. The project surrounded the main line to carry out our study work: designed and synthesized natrural nitroxide derivatives - radiation protection -anti-radiation lead drugs. First, Modify the molecular nitrogen oxygen radical to salidroside molecular skeleton, synthetic glcoside and phenol nitroxide derivative; Secondly, Comprehensive survey of radiation protection performance of salidroside nitroxide derivative in cell and animal levels, it is desirable to develop a low toxicity, efficient radiation protection drug leads. Finally, Conduct the detection cell radiation injury markers and the study for cell stress mechanism of radiation damage to clarify the mechanism of protection of natural nitroxide derivatives. Desirable to develop a low toxicity, efficient radiation protection lead drugs. We hope we can find an anti-riadiation drug have important practical applications in radiation protection, radiation therapy oncology, and the workers.

电离辐射是引起细胞损伤到整个机体功能异常甚至死亡的重要因素之一,但现有用于临床的辐射防护药物较少，仅有硫胺化合物、激素、细胞因子少数的几类.但是都由于毒副作用强使其在临床上的使用受到了限制.从现阶段国内外的相关研究工作中，天然药物活性成分因其具有来源广易获得毒性小生物相容性好等优势，是开发辐射防护药物研究的热点。. 本项目围绕苷类及酚类天然产物的氮氧自由基衍生物的设计合成-辐射防护性能-抗辐射先导药物这一主线开展本项研究工作。首先将氮氧自由基分子修饰到天然分子骨架上，合成天然产物氮氧自由基衍生物；其次在细胞和动物层次上综合考察红景天苷氮氧自由基衍生物的辐射防护性能，最后通过开展细胞辐射损伤标志物检测，研究细胞辐射损伤的应激机制，阐明红景天苷氮氧自由基衍生物的防护机理。期望开发一种低毒高效的辐射防护先导药物。在放射治疗肿瘤太空宇航员以及从事辐射工作人员等的辐射防护方面具有实际应用。

本项目设计合成了一系列氮氧自由基标记天然产物衍生物，考虑白藜芦醇、红景天苷、维生素E是一类天然产品，价格低廉毒性低，且已被广泛用于各种人类健康食品补充剂，而氮氧自由基本身表现出显著的辐射保护能力。这些氮氧自由基衍生物被作为活性氧物种（ROS）清除剂进行研究，以保护细胞由于X射线辐照引起的电离辐射。实验结果表明，与阳性对照药物氨磷汀相比，白藜芦醇氮氧自由基衍生物在清除由于辐照引起的细胞内活性氧物种效率更高。这些新的衍生物还可以缓解细胞活力、细胞增殖和细胞凋亡。进一步的机理研究表明，这种新型衍生物的抗辐射保护作用主要与调节凋亡蛋白的表达有关，包括cIAP-1、cIAP-2、细胞色素c、caspase-3和caspase-9。总之，氮氧自由基标记白藜芦醇衍生物有可能作为有效的放射性保护剂，减轻由于电离辐射引起的机体损伤，我们相信，这项工作为氮氧自由基作为新的安全有效的放射性保护剂候选者提供了强有力的理论参考和实验基础。关于进一步评估这些衍生物的体外工作仍在我们小组中开展。