Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland.
Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland.
Eur J Med Chem. 2018 Aug 5;156:13-20. doi: 10.1016/j.ejmech.2018.06.057. Epub 2018 Jun 25.
Piperlongumine, also known as piplartine, is an amide alkaloid of Piper longum L. (long piper), a medical plant known from Ayurvedic medicine. Although was discovered well over fifty years ago, its pharmacological properties have been uncovered in the past decade. In particular, piperlongumine has been most extensively studied as a potential anticancer agent. Piperlongumine has exhibited cytotoxicity against a broad spectrum of human cancer cell lines, as well as demonstrated antitumor activity in rodents. Piperlongumine has also been found to be a proapoptotic, anti-invasive, antiangiogenic agent and synergize with modern chemotherapeutic agents. Because of its clinical potential, several studies were undertaken to obtain piperlongumine analogues, which have exhibited more potent activity or more appropriate drug-like parameters. In this review, the synthesis of piperlongumine analogues and piperlongumine-based hybrid compounds, as well as their anticancer properties and the molecular basis for their activity are explored. General structure-activity relationship conclusions are drawn and directions for the future research are indicated.
千里光碱，也称为千里光宁，是一种酰胺生物碱，来源于胡椒科植物 Piper longum L.（长胡椒），这种药用植物源自阿育吠陀医学。尽管它早在五十多年前就被发现了，但在过去十年中才揭示了其药理学特性。特别是，千里光碱作为一种潜在的抗癌药物已得到广泛研究。千里光碱对多种人类癌细胞系具有细胞毒性，并在啮齿动物中表现出抗肿瘤活性。千里光碱还被发现具有促凋亡、抗侵袭、抗血管生成作用，并与现代化疗药物具有协同作用。由于其临床潜力，已经进行了几项研究来获得千里光碱类似物，这些类似物表现出更强的活性或更合适的药物样参数。在这篇综述中，探讨了千里光碱类似物和基于千里光碱的杂合化合物的合成，以及它们的抗癌特性和它们活性的分子基础。得出了一般的构效关系结论，并指出了未来的研究方向。
