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深海天然产物的化学计量学分析。

A Chemometric Analysis of Deep-Sea Natural Products.

机构信息

School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand.

出版信息

Molecules. 2019 Oct 31;24(21):3942. doi: 10.3390/molecules24213942.

Abstract

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 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 and 2/3 were within Known Drug Space (KDS), highlighting the high 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 chemical space and are a rich and promising source of biologically-active natural products for the purposes of drug development and therapeutic application.

摘要

深海天然产物是由独特的海洋生物在极端环境中创造的,这些环境对其居民来说极具挑战性。在这项研究中,分析了 2009 年至 2013 年期间分离出的 179 种深海天然产物的物理化学性质,这些性质是化合物 ADMET(吸收、分布、代谢、排泄和毒性)特征的重要指标。对这些分子描述符和特征的研究和分析,使这些化合物能够在各种化学空间中得到定义,特别是作为其在化学空间中的位置和特征的指示。这是首次对深海来源的天然产物进行分析。研究发现,约 40%的深海天然产物具有新颖性,2/3 的产物位于已知药物空间(KDS)内,这突出表明相当一部分深海天然产物具有较高的成药性,其中大多数已被证明具有显著的生物活性,值得进一步研究作为潜在的治疗药物。此外,这项研究还揭示了动物界、细菌和真菌生物的化合物之间的一般结构差异,结果表明,动物界成员的天然产物在结构上比细菌和真菌的化合物更为多样化。此外,还注意到,一般来说,真菌来源的化合物在化学空间中占据更有利的位置,是开发药物和治疗应用的具有生物活性的天然产物的丰富而有前途的来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2d7/6865307/8bd3fc4bff17/molecules-24-03942-g001.jpg

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