Biodiversity: A continuing source of novel drug leads
Biodiversity: A continuing source of novel drug leads
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DOI：
10.1351/pac200577010007
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发表时间：
2005-01-01
影响因子：
1.8
通讯作者：
Newman, DJ
中科院分区：
文献类型：
--
作者：
Cragg, GM;Newman, DJ
几千年来，大自然一直是药物的来源，并继续是新的化学类型和药效团的丰富来源。由于对大约25万种高等植物中只有5%到15%的物种进行了系统的调查，而且几乎没有挖掘海洋环境的潜力，这些地区仍将是新的生物活性化合物的丰富来源。目前已知的细菌物种不到1%，真菌物种不到5%，新微生物来源的潜力似乎是无限的，特别是那些在极端环境中发现的微生物来源。除了这些自然来源，还可以通过基因工程在某些类别的微生物代谢物中研究新结构类型的合理设计。显然，大自然可以通过组合方法(化学和生化)为精制提供新的化学支架，从而导致根据其药理活性进行优化的试剂。已证实的天然产品药物发现记录，再加上陆地和海洋生态系统的破坏对生物多样性的持续威胁，以及目前制药工业管道中新的化学实体数量较少，提供了一个令人信服的论点，支持扩大多学科和国际合作，探索将自然作为开发药物和其他有价值的生物活性物质的新线索的来源。
Nature has been a source of medicinal agents for thousands of years and continues to be an abundant source of novel chemotypes and pharmacophores. With only 5 to 15% of the approximately 250 000 species of higher plants systematically investigated, and the potential of the marine environment barely tapped, these areas will remain a rich source of novel bioactive compounds. Less than 1% of bacterial and 5% of fungal species are currently known, and the potential of novel microbial sources, particularly those found in extreme environments, seems unbounded. To these natural sources can be added the potential to investigate the rational design of novel structure types within certain classes of microbial metabolites through genetic engineering. It is apparent that Nature can provide the novel chemical scaffolds for elaboration by combinatorial approaches (chemical and biochemical), thus leading to agents that have been optimized on the basis of their pharmacological activities. The proven natural product drug discovery track record, coupled with the continuing threat to biodiversity through the destruction of terrestrial and marine ecosystems and the current low number of new chemical entities in pharmaceutical industry pipelines, provides a compelling argument in favor of expanded multidisciplinary and international collaboration in the exploration of Nature as a source of novel leads for the development of drugs and other valuable bioactive agents.