Alkaloids as drug leads - A predictive structural and biodiversity-based analysis
Alkaloids as drug leads - A predictive structural and biodiversity-based analysis
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DOI：
10.1016/j.phytol.2014.06.015
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发表时间：
2014-12-01
影响因子：
1.7
通讯作者：
Heinrich, Michael
中科院分区：
文献类型：
--
作者：
Amirkia, Vafa;Heinrich, Michael
药物的发现和开发过程，特别是天然产物的发现和开发过程，在过去30年中已明显演变为越来越公式化的方法。作为一大类天然产品，早在4000年前就被发现和使用，生物碱及其衍生的物种已在世界范围内被用作治疗各种疾病的药物来源。然而，在它们的历史意义和它们在现代药物开发中的出现之间存在着巨大的差异。生物碱在现代医学中被低估了吗？来自天然产物词典的27,683种生物碱的物理化学特征与来自不同数据库（包括欧洲生物信息学研究所的ChEMBL和全球生物多样性信息设施的GBIF）的药理学显著性和其他指标进行了交叉参考。我们首次表明，一类化合物的市场/发展表现与其生物多样性分布（由GBIF数据集定义）有关。这种大规模数据分析的潜力是针对用于指导药物发现过程的普遍规则和天然产品开发的更大背景进行分析的。(C) 2014年作者。欧洲植物化学学会。这是一篇基于CC by许可的开放获取文章。
The process of drug discovery and development particularly that of natural products, has evolved markedly over the last 30 years into increasingly formulaic approaches. As a major class of natural products initially discovered and used as early as 4000 years ago, alkaloids and the species they are derived from have been used worldwide as a source of remedies to treat a wide variety of illnesses. Yet, a tremendously wide discrepancy between their historical significance and their occurrence in modern drug development exists. Are alkaloids underrepresented in modern medicine?The physicochemical features of 27,683 alkaloids from the Dictionary of Natural Products were cross-referenced to pharmacologically significant and other metrics from various databases including the European Bioinformatics Institute's ChEMBL and Global Biodiversity Information Facility's GBIF. For the first time we show that market/developmental performance of a class of compounds is linked to its biodiversity distributions, as defined by the GBIF dataset. The potential of such a large-scale data analysis is analyzed against both prevalent rules used to guide drug discovery processes and the larger context of natural product development. (C) 2014 The Authors. Phytochemical Society of Europe. Published by Elsevier B.V. This is an open access article under the CC BY license.