桃金娘科药用植物中新型间苯三酚类成分的发现及其抑制血管新生作用研究

项目名称： 桃金娘科药用植物中新型间苯三酚类成分的发现及其抑制血管新生作用研究

项目编号： No.U1401225

项目类型： 联合基金项目

立项/批准年度： 2015

项目学科： 管理科学

项目作者： 叶文才

作者单位： 暨南大学

项目金额： 243万元

中文摘要： 恶性肿瘤严重地威胁人类生命健康。以抑制肿瘤血管新生为靶标的抗肿瘤药物因其可特异性地作用于肿瘤组织，对正常组织损伤较小，已成为抗肿瘤药物研究领域的热点之一。其中，阻断或干扰血管内皮生长因子及其特异性受体(VEGF/VEGFR)信号通路的转导是血管新生抑制剂类抗肿瘤药物研发的重要方向。本课题组在前期研究中，从3种岭南地区的桃金娘科药用植物中分离鉴定出一系列结构新颖的间苯三酚类成分，其中部分化合物可显著地抑制鸡胚尿囊血管的新生，且毒性较小。初步的作用机制研究表明，该类成分抑制血管新生作用与VEGF/VEGFR通路有关。本项目拟在前期工作基础上，选择桃金娘等6种桃金娘科药用植物对其间苯三酚类成分进行系统分离，评价和研究该类成分抑制肿瘤血管新生的生物活性、构效关系及作用机制，并对一些活性显著、毒副作用小的先导物开展成药性评价，为研发小分子血管新生抑制剂类抗肿瘤药物提供科学依据。

中文关键词： 桃金娘科；间苯三酚类成分；抑制血管新生；抗肿瘤；作用机制

英文摘要： Cancer is one of the major causes of death. Angiogenesis, the process by which new blood vessels develop from pre-existing vasculature, plays an important role in tumor growth, invasion and metastasis. Recently, targeting angiogenesis becomes an attractive therapeutic strategy in the treatment of cancer. Angiogenesis is a complex process regulated by multiple growth factors and cytokines. Among them, vascular endothelial growth factor (VEGF)/VEGF receptors-signaling pathway is one of the most important target as anti-angiogenic therapeutics for the treatment of cancer. Our previous phytochemical investigations on three species of medicinal plants of family Myratceae had resulted in the isolation of a series of novel phloroglucinol compounds, some of which showed significant anti-angiogenic effect in chick embryo chorioallantoic menbrance model with lower toxicity on the normal cells. The preliminary mechanism study indicated that VEGF/VEGFRs-signaling pathway should be implicated in the anti-angiogenic effect of these phloroglucinol compounds. Based on the previous study, we planning to carry out systematic chemical studies on six selected species of medicinal plants of family Myratceae to obtain much more phloroglucinol compounds. Furthermore, the biological activities of those phloroglucinol compounds on anti-angiogenic effects, as well as their structure-activity relationship and action mechanism will also be investigated. Active compounds with higher selectivity and lower toxicity will be further investigated for their medicinal properties. Our findings could be used as scientific evidence for the new drug development of anti-angiogenic therapeutics for the treatment of cancer.

英文关键词： Myrtaceae;phloroglucinol compounds;anti-angiogenesis;antitumor;action mechanism