Uridine natural products: Challenging targets and inspiration for novel small molecule inhibitors.
Nucleoside derivatives, in particular those featuring uridine, are familiar components of the nucleoside family of bioactive natural products. The structural complexity and biological activities of these compounds have inspired research from organic chemistry and chemical biology communities seeking to develop novel approaches to assemble the challenging molecular targets, to gain inspiration for enzyme inhibitor development and to fuel antibiotic discovery efforts. This review will present recent case studies describing the total synthesis and biosynthesis of uridine natural products, and de novo synthetic efforts exploiting features of the natural products to produce simplified scaffolds. This research has culminated in the development of complementary strategies that can lead to effective uridine-based inhibitors and antibiotics. The strengths and challenges of the juxtaposing methods will be illustrated by examining select uridine natural products. Moreover, structure-activity relationships (SAR) for each natural product-inspired scaffold will be discussed, highlighting the impact on inhibitor development, with the aim of future uridine-based small molecule expansion.
['Arbour|Christine A|CA|', 'Imperiali|Barbara|B|']
D000900:Anti-Bacterial Agents D001688:Biological Products D055808:Drug Discovery D004791:Enzyme Inhibitors D006801:Humans D015394:Molecular Structure D010710:Phosphates D000081026:Polyprenols D013329:Structure-Activity Relationship D014529:Uridine
Uridine Structure-activity relationship Inhibitor discovery Natural product antibiotics Nucleoside analog