Scaffold architecture and pharmacophoric properties of natural products and trade drugs: Application in the design of natural product-based combinatorial libraries

Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural simila rity. Several such potential scaffolds for combinatorial chemistry were ide ntified that are not present in current trade drugs. For one of these scaff olds a virtual combinatorial library was generated. Pharmacophoric properti es of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs a nd natural products have several topological pharmacophore patterns in comm on. These features can be systematically explored with selected combinatori al libraries based on a combination of natural product-derived and syntheti c molecular building blocks.