The essence of enzymes is to maintain the normal activities of living organisms by catalyzing metabolic reactions and regulating cells. Inhibiting enzyme activity can slow the progression of certain diseases and cure them, making enzymes one of the major targets for disease treatment. The search and development of novel enzyme inhibitors are of great significance for the treatment of certain major diseases. One of the most prominent features of natural products is their complex and diverse structures, which often compliments the synthetic capabilities of medicinal chemistry. Considering the biosynthetic processes of natural molecules in organisms, they exhibit higher similarity and binding potential with biological structures, enabling them to serve as ligands for various enzymes and receptors. In this review, we summarized a total of 226 novel natural products with enzyme inhibitory activity published in 49 articles over the past three years (2022-2024). These natural products (including terpenes, alkaloids, flavonoids, phenylpropanoids, polyketides, peptides, anthraquinones, etc.) are derived from plants, microorganisms, and marine organisms. We also discuss some synthetic analogs, with a focus on their structures and biological activities. This review provides useful information for the research and development of novel enzyme inhibitors.
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