Rediscovery of known natural compounds: Nuisance or goldmine?
Rediscovery of known natural compounds: Nuisance or goldmine?
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DOI：
10.1016/j.bmc.2005.05.067
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发表时间：
2005-09-01
影响因子：
3.5
通讯作者：
Bohlin, L
中科院分区：
文献类型：
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作者：
Tulp, M;Bohlin, L
是否所有天然化合物都具有独特的生物活性，或者它们中的大多数仅仅是生物合成碎片？许多天然化合物都具有重要的生物功能，目前已知的 200,000 多种天然化合物中当然还有更多，最终将被证明不仅仅是“次级代谢产物”。问题是如何为潜在新药选择最有前途的候选药物。参与新化合物鉴定的科学家认为“重新发现”已知天然化合物是一件令人烦恼或令人失望的事情。然而，硬币的另一面是，在不相关的物种中发现特定化合物可能是识别新受体或酶的宝贵线索。在这里，我们提出了这样的假设：当一种天然化合物出现在不相关的物种中时，它一定通过与特定的分子靶标相互作用而具有重要的生物学功能。这是因为在自然界中，一种特定的化合物是完全不相关的物种无缘无故地合成的，这是极其不可能的。对于不相关物种中存在的许多化合物，已知它们作用于特定的分子靶标。对于其他人来说，只知道它们出现在不同的物种中。在某些情况下，生物活性是已知的，但其潜在的作用机制尚不清楚。正是从这类化合物中才有可能取得重要的发现。其中一些（大约 70 名）已被确认。它们代表了来自自然界的重要线索，为大量化合物的经典筛选提供了另一种方法。 (c) 2005 Elsevier Ltd. 保留所有权利。
Do all natural compounds have a distinct biological activity, or are most of them merely biosynthetic debris? Many natural compounds have important biological functions, and certainly many more of the ample 200,000 currently known will ultimately prove to be more than just 'secondary metabolites'. The question is how to select the most promising candidates for potential new drugs. 'Rediscovery' of known natural compounds is regarded as a nuisance or disappointment by scientists involved with the identification of novel compounds. The other side of the coin, however, is that the discovery that a particular compound occurs in unrelated species can be a valuable clue toward the identification of a novel receptor or enzyme. Here, we put forward the hypothesis that when a natural compound occurs in unrelated species, it must have an important biological function by interacting with a specific molecular target. This is because it is extremely improbable that in nature one particular compound is synthesized in totally unrelated species for no reason at all. For many compounds occurring in unrelated species, it is already known that they act on specific molecular targets. For others, it is just known that they occur in different species. In some cases, biological activities are known but not the underlying mechanisms of action. It is from this category of compounds that important discoveries are likely to be made. Some (around 70) of them were identified. They represent important clues from nature offering an alternative approach to the classical screening of large numbers of compounds. (c) 2005 Elsevier Ltd. All rights reserved.