Drug discovery inspired by bioactive small molecules from nature

Abstract

Natural products (NPs) have greatly contributed to the development of novel treatments for human diseases such as cancer, metabolic disorders, and infections. Compared to synthetic chemical compounds, primary and secondary metabolites from medicinal plants, fungi, microorganisms, and our bodies are promising resources with immense chemical diversity and favorable properties for drug development. In addition to the well-validated significance of secondary metabolites, endogenous small molecules derived from central metabolism and signaling events have shown great potential as drug candidates due to their unique metaboliteprotein interactions. In this short review, we highlight the values of NPs, discuss recent scientific and technological advances including metabolomics tools, chemoproteomics approaches, and artificial intelligence-based computation platforms, and explore potential strategies to overcome the current challenges in NP-driven drug discovery.