title: Overview of the therapeutic potential of piplartine (piperlongumine).
abstract: Piplartine (piperlongumine, 5,6-dihydro-1-[(2E)-1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)-pyridinone) is a biologically active alkaloid/amide from peppers, as from long pepper (Piper longum L. - Piperaceae). Long pepper is one of the most widely used in Ayurvedic medicine, which is used to treat many diseases, including tumors. The purpose of the current paper is to address to the chemical structure establishment and to systematically survey the published articles and highlight recent advances in the knowledge of the therapeutic potential of piplartine, establishing new goals for future research. The reported pharmacological activities of piplartine include cytotoxic, genotoxic, antitumor, antiangiogenic, antimetastatic, antiplatelet aggregation, antinociceptive, anxiolytic, antidepressant, anti-atherosclerotic, antidiabetic, antibacterial, antifungal, leishmanicidal, trypanocidal, and schistosomicidal activities. Among the multiple pharmacological effects of piplartine, its anticancer property is the most promising. Therefore, the preclinical anticancer potential of piplartine has been extensively investigated, which recently resulted in one patent. This compound is selectively cytotoxic against cancer cells by induction of oxidative stress, induces genotoxicity, as an alternative strategy to killing tumor cells, has excellent oral bioavailability in mice, inhibits tumor growth in mice, and presents only weak systemic toxicity. In summary, we conclude that piplartine is effective for use in cancer therapy and its safety using chronic toxicological studies should be addressed to support the viability of clinical trials.
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Sergipe, Av. Marechal Rondon, Jardim Rosa Elze, 49100-000, São Cristóvão, Sergipe, Brazil. Electronic address: danielpbezerra@gmail.com.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bezerra
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Manoel O
authors.initials: MO
authors.lastname: de Moraes
authors.affiliation: Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Nicolau
authors.initials: N
authors.lastname: Saker-Neto
authors.affiliation: Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Edilberto R
authors.initials: ER
authors.lastname: Silveira
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Leticia V
authors.initials: LV
authors.lastname: Costa-Lotufo
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001682:Biological Availability; D015507:Drugs, Investigational / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005638:Fruit / Q000737:chemistry; D006801:Humans; D008515:Medicine, Ayurvedic; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010330:Patents as Topic; D031701:Piper / Q000737:chemistry; D010881:Piperidones / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015507:Drugs, Investigational; D010881:Piperidones; C498077:piperlongumine