Therapeutic Implications of Piperlongumine

Piperlongumine (PL) is a biologically active amide alkaloid natural product obtained from long pepper, Piper longum L., belonging to the Piperaceae family, commonly used in traditional medicine. This phytochemical exhibits promising bioactivities ranging from anticancer, antibacterial, antifungal, antidiabetic, antiangiogenic, antiplatelet aggregation, senolytic, anxiolytic, antidepressant, anti-inflammatory, and antinociceptive, among others. The antitumor properties shown by PL are the most significant of all and have been validated in various cancer types in vitro or in vivo, setting a stage for promising preclinical studies. It is selectively cytotoxic against cancer cells with induction of reactive oxygen species (ROS)-mediated oxidative stress as one of the major mechanisms of action for promoting apoptosis. Several animal model research studies also report good bioavailability and negligible systemic toxicity for PL, making it a suitable lead candidate for antitumor drug development. Plethora of synthetic and structure activity relationship (SAR) studies have pointed out that PL core skeleton can be modified at several sites to make it more potent toward cancer cells as well as to improve its other pharmacological properties, such as enhancing water solubility and reducing lipophilicity. In this chapter, we summarize the structural, biochemical, and mechanistic aspects of all the reported bioactivities for PL, highlighting the fact that it could be a novel compound to be pursued for advanced clinical studies for cancer chemotherapy solely or in combination with other existing anticancer drugs in practice.