Pyrimidine-containing natural products: occurrences and biological activities

Nitrogen-containing core structure pyrimidine has long been regarded as one of the privileged scaffolds for novel drug development. Natural products embedded with pyrimidine motifs are distinguished by their exceptional scaffold diversity and vast structural complexity, which endow them with versatile biological activities, including anticancer, antiviral, antifungal and anti-inflammatory activities. This review is dedicated to surveying a series of structurally distinctive naturally occurring compounds characterized by the presence of an aromatic heterocyclic pyrimidine moiety covering from 2004 to early 2025. Multiple key aspects of these 156 pyrimidine-containing compounds, including natural sources, features of chemical structure, biological activities, as well as biosynthetic studies are summarized. The review emphasizes the enduring potential of natural products, highlighting their inherent capacity for medication and optimization to fuel the pipeline of lead compound targeting major disease and providing new window for overview of these pyrimidine-containing natural products. Overall, this review aims to unlocking the potential of these isolates. It thus offers a fresh reference for the exploitation of pyrimidine-containing natural products, with the ultimate goal of realizing their therapeutic potential.