Antibacterial natural products in medicinal chemistry - Exodus or revival?

被引:512
作者
von Nussbaum, Franz [1 ]
Brands, Michael [1 ]
Hinzen, Berthold [1 ]
Weigand, Stefan [1 ]
Haebich, Dieter [1 ]
机构
[1] Bayer HealthCare, Med Chem Europe, D-42096 Wuppertal, Germany
关键词
antibiotics; genomics; glycopeptides; natural products; total synthesis;
D O I
10.1002/anie.200600350
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.
引用
收藏
页码:5072 / 5129
页数:58
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