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 a very 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.