Natural products: a continuing source of novel drug leads.
Natural products: a continuing source of novel drug leads.
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DOI：
10.1016/j.bbagen.2013.02.008
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发表时间：
2013-06
影响因子：
3
通讯作者：
Newman, David J.
中科院分区：
文献类型：
--
作者：
Cragg, Gordon M.;Newman, David J.
几千年来，大自然一直是医药产品的来源，许多有用的药物都是从植物来源开发出来的。随着青霉素的发现，微生物来源的药物被发现，20世纪70年代的潜水技术开辟了海洋。组合化学(20世纪80年代末)，将药物发现工作的重点从自然转移到实验室。这篇综述追溯了天然产物药物的发现，概述了来自天然来源的重要药物，这些药物彻底改变了严重疾病的治疗。很明显，自然将继续是新的结构性线索的主要来源，有效的药物开发依赖于多学科的合作。基因信息的爆炸不仅导致了新的筛选，而且基因技术使得组合生物合成技术和基因组挖掘的实施成为可能。所获得的知识使未知分子得以被识别。这些新的生物活性结构可以通过组合化学来优化，从而产生治疗许多疾病的新候选药物。一般意义：允许从微生物中分离/表达生物合成盒的基因技术的出现很可能是天然产品先导发现的新前沿。现在很明显，这些生物的生物多样性可能要大得多。微生物世界中涉及的潜在物种的数量比植物和多细胞动物的数量多出许多个数量级。将这些数字与目前确定的目前未表达的生物合成簇的数量(每个物种10个)相结合，微生物多样性的潜力基本上仍未开发。
Nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. Following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from Nature to the laboratory bench. This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases. It is clear Nature will continue to be a major source of new structural leads, and effective drug development depends on multidisciplinary collaborations. The explosion of genetic information led not only to novel screens, but the genetic techniques permitted the implementation of combinatorial biosynthetic technology and genome mining. The knowledge gained has allowed unknown molecules to be identified. These novel bioactive structures can be optimized by using combinatorial chemistry generating new drug candidates for many diseases. General Significance: The advent of genetic techniques that permitted the isolation / expression of biosynthetic cassettes from microbes may well be the new frontier for natural products lead discovery. It is now apparent that biodiversity may be much greater in those organisms. The numbers of potential species involved in the microbial world are many orders of magnitude greater than those of plants and multi-celled animals. Coupling these numbers to the number of currently unexpressed biosynthetic clusters now identified (>10 per species) the potential of microbial diversity remains essentially untapped.
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影响因子：
1.5
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.2335845100
发表时间：
2003-11-25
影响因子：
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