Cheminformatics analysis of natural products: lessons from nature inspiring the design of new drugs

Abstract

Natural products (NPs) have evolved over a very long natural selection process to form optimal interactions with biological 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 more than 130,000 NP structures. The physicochemical properties of NPs and their typical structural features are compared to those of bioactive molecules and average organic molecules. The relationship between the structure of NPs and the type of organism from which they have come has also been analyzed. The aim of this study was to identify those properties and structural features which are typical for NPs and discriminate this class of molecules from common synthetic molecules, with the ultimate goal being to provide a guide for the design of novel NP-like bioactive structures. Hopefully the results of this analysis help to eliminate the old myth about NPs as being 'too complex' or having 'bad properties', as well as help us to focus on these areas of NP structural space which are essential for biological activity, taking advantage of the process of natural selection over billions of years to guide us to new and as yet unexplored areas of the Chemical Structure Universe.