【作者】 李学娟；

【导师】 张红雨；

【作者基本信息】 山东理工大学 ， 生物化学与分子生物学， 2008， 硕士

【摘要】 考虑到世界范围内的植物分布模式极其相似以及西药中包含有大量天然药物信息的事实,我们推测尽管用于治疗同一种疾病的中药和西药的植物来源不一定相同,但是二者的活性成份在分子结构上有可能是相同或相近的。这些信息不但可以证明中药疗效是有物质基础的,更为重要的是,可以用来指导组合药物设计。为了验证这一猜想,本论文借助化学信息学的方法、技术对中西药物化合物作了整体结构相似性比较。通过比较中药化学(TCMD)和综合药物化学(CMC)数据库发现结构相似性大于0.85的化合物908对,其中327对是结构完全相同的;同时,比较了中药化学(TCMD)和药物开发报道数据库(MDDR)发现结构相似性大于0.85的化合物1054对,其中146对是结构完全相同的。继之对327对化合物进行活性注释,发现一些功效的记载已经有1500年的历史。然后,我们分析了不同体系传统药物的演化历史发现。尽管东西方的医药体系相对独立发展,但在植物水平上,东西方采用同一种或同一属的某些植物药治疗相似的疾病;在分子水平上,尽管很多目前使用的分子药物不是来源于中药,但在中药植物的化学成分中发现其含有相应的活性化合物。这意味着经历了几千年演化的中、西药药学体系之间存在着趋同进化现象。最后,通过传统中药成分、天然产物、临床药物、药物候选物的化学空间分析,我们认为寻找新化学实体将越来越困难,因此,应该转变药物研发模式,通过组合现有药物来发现新药。同时,以几个中药复方为例,探讨了中西方药物的分子水平相似性在组合药物开发中的潜在应用。本研究不但加深了对药学体系演化规律的认识,提高中药在严格科学意义上的可信度;而且研究结果对于设计组合药物具有指导意义。更多还原

【Abstract】 Considering the fact that the plant distribution patterns in China and other regions of the world are rather similar and Western drugs including many natural medicine information, we speculate that although Western drugs and traditional Chinese remedies origined from different herbs to treat the same conditions, but their activity components in structure is perhaps the same or similar, this information not proved traditional Chinese medicine have good effection, most importantly , it can guide the design of new combinatorial drugs.To verify this speculation, we employed chemoinformatic methods to make a global structural comparison between～10,000 traditional Chinese medicine (TCM) components (recorded in traditional Chinese Medicine Database (TCMD)) and～8,000 modern Western drugs (recorded in Comprehensive Medicinal Chemistry (CMC) database), which revealed that 908 agent pairs are structurally similar (with similarity≥0.85). Among them, 327 agent pairs are identical in structures. Furthermore, a comparison between～10,000 TCM components and～145,000 drug candidates (recorded in MDL Drug Data Report (MDDR) database) identified 1,054 pairs of structurally similar agents (with similarity≥0.85). Among them, 146 agent pairs are identical in structures. It is interesting to note that a certain part of CMC counterparts of TCMD agents recorded in ancient Chinese medicinal book for more than 1500 years.Secondly through comparing the herbal usage of ancient medicinal systems of different nations, we noticed that some similar herbs have been independently discovered and utilized to treat similar diseases by different cultures at herbal medicine level. At molecular level although different folks used distinct herbs to treat the same conditions, similar effective agents are responsible, at least in part, for these herbal effects. Since there was little medicinal communication between China and foreign countries 2000 years ago, we think that the existence of similar herbs and/or components in very ancient Chinese and Western medicines can be best explained as a convergent evolution in both medicinal systems.Thirdly, we compared chemical space with the components contained in traditional medicines and natural products and taked some traditional Chinese formulae example, discussed western healers in traditional Chinese medicine of implications for finding Western drug combinations.This research not deepen understand evolvement between two medicinal systems, improve the reliability for traditional Chinese medicine in science point of view, but the result can apply to synergistic combined drugs, and guide the discovery of new combined drugs.更多还原