Cheminformatics Analysis of Natural Product Scaffolds: Comparison of Scaffolds Produced by Animals, Plants, Fungi and Bacteria

Abstract

Natural products (NPs) have evolved over a very long natural selection process to form optimal interactions with biologically relevant macromolecules. NPs are therefore an extremely useful source of inspiration for the design of new drugs. In the present study we report the results of a cheminformatics analysis of a large database of NP structures focusing on their scaffolds. First, general differences between NP scaffolds and scaffolds from synthetic molecules are discussed, followed by a comparison of the properties of scaffolds produced by different types of organisms. Scaffolds produced by plants are the most complex and those produced by bacteria differ in many structural features from scaffolds produced by other organisms. The results presented here may be used as a guidance in selection of scaffolds for the design of novel NP-like bioactive structures or NP-inspired libraries.

Substituents of life: The most common substituent patterns present in natural products

“…The heights of the bars in the graph are proportional to the relative frequencies of the particular substituents in these 3 sets. As one could expect, the distribution of substituents in different sets is quite different, with the NP substituents being a clear outlier, as already discussed in the previous analysis.. Fig,4. Relative frequencies of common substituents present in natural products (green), bioactive molecules (blue) and common synthetic molecules (orange).…”

Substituents of life: The most common substituent patterns present in natural products

“…It is well known that the structures of natural products (NPs) differ considerably from those of synthetic molecules [1]. This has been documented by several publications focusing on general substructure features [2], scaffolds [3,4] or functional groups [5]. So far, however, no study focused on the detailed analysis of substituents typical for NPs has been performed.…”

NP Navigator: a New Look at the Natural Product Chemical Space

“…Different methods are suitable for this task and a lot of them have been already used to analyze libraries of compounds of natural origin 25 . Principal component analysis (PCA) 26 and scaffold trees 27 were most often used, but self-organizing maps 28 and generative topographic mapping (GTM) 29 were also applied. Most of the numerous articles in this field simply report static results of particular compound library analysis, not allowing readers to explore the chemical space of NPs by themselves.…”