College of Pharmaceutical Sciences , Zhejiang University , Hangzhou , Zhejiang 310058 , China.
State Key Laboratory of Agricultural Microbiology and Agricultural Bioinformatics, Key Laboratory of Hubei Province, College of Informatics , Huazhong Agricultural University , Wuhan 430070 , China.
J Chem Inf Model. 2018 Jun 25;58(6):1182-1193. doi: 10.1021/acs.jcim.8b00125. Epub 2018 Jun 7.
This is a new golden age for drug discovery based on natural products derived from both marine and terrestrial sources. Herein, a straightforward but important question is "what are the major structural differences between marine natural products (MNPs) and terrestrial natural products (TNPs)?" To answer this question, we analyzed the important physicochemical properties, structural features, and drug-likeness of the two types of natural products and discussed their differences from the perspective of evolution. In general, MNPs have lower solubility and are often larger than TNPs. On average, particularly from the perspective of unique fragments and scaffolds, MNPs usually possess more long chains and large rings, especially 8- to 10-membered rings. MNPs also have more nitrogen atoms and halogens, notably bromines, and fewer oxygen atoms, suggesting that MNPs may be synthesized by more diverse biosynthetic pathways than TNPs. Analysis of the frequently occurring Murcko frameworks in MNPs and TNPS also reveals a striking difference between MNPs and TNPs. The scaffolds of the former tend to be longer and often contain ester bonds connected to 10-membered rings, while the scaffolds of the latter tend to be shorter and often bear more stable ring systems and bond types. Besides, the prediction from the naïve Bayesian drug-likeness classification model suggests that most compounds in MNPs and TNPs are drug-like, although MNPs are slightly more drug-like than TNPs. We believe that MNPs and TNPs with novel drug-like scaffolds have great potential to be drug leads or drug candidates in drug discovery campaigns.
这是基于海洋和陆地来源的天然产物的新药发现的黄金时代。在此，一个直接但重要的问题是“海洋天然产物（MNPs）和陆地天然产物（TNPs）的主要结构差异是什么？”为了回答这个问题，我们分析了这两类天然产物的重要物理化学性质、结构特征和类药性，并从进化的角度讨论了它们的差异。一般来说，MNPs 的溶解度较低，通常比 TNPs 更大。平均而言，特别是从独特片段和支架的角度来看，MNPs 通常具有更多的长链和大环，特别是 8 到 10 元环。MNPs 还含有更多的氮原子和卤素，特别是溴，以及较少的氧原子，这表明 MNPs 可能通过比 TNPs 更多样化的生物合成途径合成。对 MNPs 和 TNPS 中经常出现的 Murcko 框架的分析也揭示了 MNPs 和 TNPs 之间的显著差异。前者的支架往往更长，并且经常含有连接到 10 元环的酯键，而后者的支架往往更短，并且经常具有更稳定的环系统和键类型。此外，基于朴素贝叶斯类药性分类模型的预测表明，MNPs 和 TNPs 中的大多数化合物都是类药的，尽管 MNPs 比 TNPs 稍微更具类药性。我们相信具有新型类药性支架的 MNPs 和 TNPs 在药物发现活动中具有成为药物先导化合物或候选药物的巨大潜力。
