Altmann Karl-Heinz
Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences Vladimir-Prelog-Wag 4 HCI H 405 CH-8093 Zurich;, Email:
Chimia (Aarau). 2017 Oct 25;71(10):646-652. doi: 10.2533/chimia.2017.646.
The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.
海洋环境中蕴藏着大量物种，它们是各种结构多样的生物活性次生代谢产物的来源。目前，已知大约有27000种海洋天然产物，其中有8种是（曾经是）7种已上市药物的来源，这些药物主要用于治疗癌症。这些药物以及目前正在进行临床评估的大多数候选药物（不包括抗体药物偶联物）都是未修饰的天然产物，但合成化学在除一种已获批的海洋来源药物之外的所有药物的发现和/或开发过程中都发挥了核心作用。在过去十年中，每年分离出的新海洋天然产物超过1000种，但新的独特结构库远未枯竭。要充分利用海洋产生的次生代谢产物结构多样性为药物发现提供的潜力，需要对其不同生物活性进行广泛评估，并在新的发酵技术、有机合成化学和药物化学之间进行有效的相互作用，以确保化合物供应并实现先导化合物优化。
