Complexity-to-Diversity

A New Drug Discovery Paradigm

High-throughput screening (HTS) of ‘drug-like’ compound libraries has become a critical source of new drugs being brought to market. Despite the many discoveries attributed to HTS, compound libraries are known to lack small molecules that have an abundance of structural complexity (stereochemistry, fused ring systems, etc.). Compound libraries that are “deficient” in small molecule diversity will continue to yield less than ideal drug discovery campaigns.

Complexity-to-Diversity is a paradigm-shifting drug discovery approach that uses natural products as synthetic starting materials to rapidly generate chemically unrelated small molecules with diverse and complex structures for screening libraries. Our group has selected several complex natural products and we are currently working to develop highly efficient synthetic pathways that allow us to maximize ring distortion in the discovery of new hit compounds for development. Currently, we are using this Complexity-to-Diversity approach as a platform to discovery novel anticancer and antibacterial agents in collaboration with other drug discoverers here at the University of Florida and the Center for Natural Products, Drug Discovery and Development (CNPD3).

Complexity-to-Diversity Strategy for Drug Discovery

Rapid_Generation_of_Diverse_and_Complex_Scaffolds_for_Drug_Discovery

Publication from Postdoctoral Studies (with Professor Paul Hergenrother at UIUC):

  • Huigens III, R.W.; Morrison, K.C.; Hicklin, R.W.; Flood Jr., T.A.; Richter, M.F.; Hergenrother, P.J. “A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products.” Nature Chem. 2013, 5, 195-202.

Keywords: complex natural products, ring distortion, drug discovery, anticancer discovery, antibacterial discovery, chemical biology