A Chemometric Analysis of Deep-Sea Natural Products
A Chemometric Analysis of Deep-Sea Natural Products
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DOI：
10.3390/molecules24213942
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发表时间：
2019-11-01
期刊：
影响因子：
4.6
通讯作者：
Pilkington, Lisa I.
中科院分区：
文献类型：
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作者：
Pilkington, Lisa I.
深海天然产品是由独特的海洋生物创造的，这些生物在极端条件的挑战性环境中茁壮成长。在这项研究中，对2009年至2013年分离的179种深海天然产品进行了研究，分析了它们的理化性质，这些性质是化合物的ADMET（吸收、分布、代谢、排泄和毒性）特征的重要指标。通过对这些分子描述符和特征的研究和分析，确定了这些化合物在各种化学空间中的位置，特别是表明了它们的药物相似性和在化学空间中的位置，这是首次对深海衍生天然产品进行分析。研究发现，所有深海天然产物中有40%是药物样的，2/3在已知药物空间（KDS）内，突出了相当大比例的深海天然产物的高药物样性，其中大多数已经被证明具有显着的生物活性，应进一步研究作为潜在的治疗方法。此外，这项研究能够揭示来自动物界，细菌和真菌有机体的化合物之间的一般结构差异，其中观察到来自动物界成员的天然产物在结构上比来自细菌和真菌的化合物更加多样化。还注意到，一般而言，真菌衍生化合物在类药物化学空间中占据更有利的地位，是用于药物开发和治疗应用的生物活性天然产物的丰富和有前途的来源。
Deep-sea natural products have been created by unique marine organisms that thrive in a challenging environment of extreme conditions for its inhabitants. In this study, 179 deep-sea natural products isolated from 2009 to 2013 were investigated by analysing their physicochemical properties that are important indicators of the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) profile of a compound. The study and analysis of these molecular descriptors and characteristics enabled the defining of these compounds in various chemical spaces, particularly as an indication of their drug-likeness and position in chemical space and is the first to be conducted to analyse deep-sea derived natural products. It was found that 40% of all deep-sea natural products were drug-like and 2/3 were within Known Drug Space (KDS), highlighting the high drug-likeness of a significant proportion of deep-sea natural products, most of which have already been shown to have notable biological activities, that should be further investigated as potential therapeutics. Furthermore, this study was able to reveal the general structural differences between compounds from Animalia, Bacteria and Fungi organisms where it was observed that natural products from members of the Animalia kingdom are structurally more varied than compounds from bacteria and fungi. It was also noted that, in general, fungi-derived compounds occupy a more favourable position in drug-like chemical space and are a rich and promising source of biologically-active natural products for the purposes of drug development and therapeutic application.