Recent advances in piperine and its derivatives as potential anticancer agents

Piperine, a crucial ingredient of the plant Piper nigrum, exhibits a broad spectrum of biological activities and has attracted interest as a potential anticancer agent. Owing to its low yield in natural resources, chemists have developed several synthetic methods for piperine. In addition, the low water solubility and poor bioavailability of piperine have significantly limited its therapeutic applications. Structural modification, particularly at its piperidine moiety, enables the introduction of diverse functional groups to afford piperine derivatives with improved anticancer potency and favorable pharmacodynamic profiles. This article reviews the recent advances (from 2012 to 2025) in the structural characterization, chemical synthesis, biosynthesis, anticancer profile, structural modification, and structure-activity relationships of piperine, which may provide a useful direction for the development of more effective piperine-based anticancer candidates or agents.