几种滇产樟科药用植物中panamonane 类新骨架化合物的发现和活性研究

Natural products frequently possess highly selective and specific biological activities and continue to provide a diverse and unique source of bioactive lead compounds for drug discovery. A striking illustration is the influence of natural products on many of the molecular processes operative in cell cycle progression. Almost 50% of new drugs introduced during 1981-2010 had a natural product origin. In the case of anticancer and anti-infective agents, almost two-thirds of such agents are derived from natural products. .In our previous study, novel homogentisic acid-related derivatives with a unique C18 carbon skeleton were isolated from the leaves and twigs of Litsea panamonja (Nees) Hook. f. The new compounds possess an unprecedented C18 carbon skeletons that has not been reported previously from nature, which was featured with a characteristic tetrahydrobenzofuran-2,5 (3H,6H)-dione moiety and a biosynthetically extended geranyl side chain. We have designated this structural type as "panamonane". The isolates were evaluated for cytotoxic activities against human tumor cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480 and showed potential cytotoxic activities. .In this project, Based on species diversity of Lauraceae plants in Yunnan and the relationship between traditional Chinese medicine and system biology due to the similarity of species, systemic phytochemical research will be carried out on some plants of Litseae collected from Yunnan Province. Cell-line cytotoxicity screen for in vitro Assays and Human tumor xenograft models for in vivo Assays are used for further evaluation of the antitumor potential of natural products identified from Litseae. We hope to find further panamonanes and elucidate the relationship between structural characteristics and bioactivities of panamonanes.

天然产物具有化学结构多样性、生物活性多样性和类药性，已成为发现新药或药物先导化合物的重要源泉。前期研究中，我们首次从滇产樟科植物香花树中发现一类具有C18 的新骨架化合物，命名为"香花烷"（panamonane）。我们检测了其中二种香花烷分子对5 种人源肿瘤细胞的体外抗肿瘤活性。初步的活性实验表明，我们首次发现的香花烷新骨架分子具有较好的肿瘤细胞生长抑制活性。.本项目拟在前期研究基础上，将对几种亲缘关系较近的樟科木姜子族药用植物进行系统深入的研究，执行生物活性跟踪并结合化学导向的研究路线，开展植物化学成分和药效学研究，发现"香花烷"新骨架化合物，阐明该类化合物分子的结构特征，并通过系统的生理活性筛选研究，对香花烷panamonane 新骨架分子的结构特征及活性进行深入研究，以揭示该类化合物的结构－生物活性相关性。并有可能在此基础上发现活性先导化合物，为新药研究提供化学物质基础和科学依据。

自然是人类药物发现的源泉，其所蕴含的天然产物具有化学结构多样性、生物活性多样性和类药性，是发现新药或药物先导化合物的重要源泉。前期研究中，我们首次从滇产樟科植物香花树中发现一类具有C18 的新骨架化合物，命名为“香花烷”（panamonane）。本项目在前期研究基础上，通过研究阐明了“香花烷”新骨架化合物的结构归属于一类混源萜新结构骨架，并进一步阐明了其分子结构特征。并对5种亲缘关系较近的樟科木姜子族药用植物进行了系统深入的研究，采用各种色谱技术，利用各种现代波谱技术和计算方法鉴定了所分离化合物的结构，共分离鉴定160个单体化合物，化合物类型涉及萜类、异喹啉生物碱、内酯类、酰胺、萜类、木脂素、黄酮及其甙类化合物。化学成分的研究有助于阐明木姜子源植物的化学物质基础和药效学基础，新骨架和新化合物的发现丰富了天然产物的内容，为木姜子源植物的化学分类学提供了科学依据。在民间药用特点和相关药理学文献报道基础上，对己分离鉴定的化学成分和主要提取部位重点开展了抗肿瘤、抗炎、抗HIV等体内体外活性评价，从中发现了具有较好抗肿瘤、抗炎、抗HIV活性的分子和部位。活性化合物的发现，为阐明木姜子源植物的药效学基础提供了科学依据，活性化合物作为先导化合物有利于指导今后进一步开展的结构修饰改造和活性研究，为深入研究和开发利用木姜子源植物奠定了科学基础。研究结果表明木姜子源植物是新结构和新活性物质的重要来源，是寻找药物先导化合物的重要资源。