Editorial [Hot Topic: Natural Product Inspired Small Molecular Scaffolds in Anticancer Therapy (Guest Editor: Jetze J. Tepe)]

Natural products isolated from plant, animal or fermentation have long been the main source for the chemotherapeutic intervention of cancer. However, in the later part of the 20th century, the advances of combinatorial chemistry have taken centerstage in the drug discovery process and natural product synthesis took a temporary backseat for these new chemical processes. Combinatorial techniques have resulted into large libraries in a very cost-efficient manner that can be screened for their biological activities. However, only a surprising low number of compounds found in such libraries have advanced to an FDA approved drug. This relative low success rate is primarily due to the lack of diveristy of new scaffolds with respect to their structural complexity, stereochemistry and chemical space. During the last decade, diversity oriented synthesis of small molecule libraries has become increasingly important in the search and development of new pharmaceutical leads. New synthetic methods are allowing for efficient and rapid production of highly diverse libraries of small yet complex molecules that can be screened for biological relevance. Screening of these libraries does not only lead to the identification of new drug leads, but also to potential new therapeutic protein targets and protein-drug interaction. These new leads can subsequently be optimized, by combinatorial chemistry, to generate new drug candidates. In order to maximize the potential of new scaffold libraries, the combination of natural product synthesis and diveristyoriented synthesis has resulted in a renewed focus on natural product inspired design of small molecule scaffolds. In this approach, common structural features found in natural product pharmacophores, are incorporated in a new scaffold libraries and tested for its biological relevance. In this context, the present issue highlights some of the recent trends with emphasis on natural product inspired scaffold syntheses.