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Piperlongumine (Piplartine) is an naturally occurring and biologically active alkaloid that has been isolated from peppers, particularly long peppers like Piper longum Linn. It has anti-inflammatory, antibacterial, antiangiogenic, antioxidant, antitumor, and anti-diabetic properties. In cancer cell lines, piperlongumine causes the production of ROS and apoptosis. Piperlongumine inhibits myofibroblast transformation by blocking the ERK1/2 signaling pathway and exhibits anti-cardiac fibrosis activity. Ayurvedic medicine, which is used to treat a variety of illnesses, including tumors, uses long pepper as one of its most popular herbs. The pharmacological effects of piplartine have been described as including cytotoxic, genotoxic, antitumor, antiangiogenic, antimetastatic, antiplatelet aggregation, antinociceptive, anxiolytic, antidepressant, anti-atherosclerotic, antidiabetic, antibacterial, antifungal, leishmanicidal, trypanocidal, and schistosomicidal effects. The most promising of piplartine's numerous pharmacological effects is its ability to fight cancer.
Physicochemical Properties
| Molecular Formula | C17H19NO5 |
| Molecular Weight | 317.3365 |
| Exact Mass | 317.126 |
| Elemental Analysis | C, 64.34; H, 6.03; N, 4.41; O, 25.21 |
| CAS # | 20069-09-4 |
| Related CAS # | 20069-09-4 |
| PubChem CID | 637858 |
| Appearance | White to yellow solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 475.6±45.0 °C at 760 mmHg |
| Melting Point | 124ºC |
| Flash Point | 241.4±28.7 °C |
| Vapour Pressure | 0.0±1.2 mmHg at 25°C |
| Index of Refraction | 1.581 |
| LogP | 2.34 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 23 |
| Complexity | 473 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O(C([H])([H])[H])C1C(=C(C([H])=C(C=1[H])/C(/[H])=C(\[H])/C(N1C(C([H])=C([H])C([H])([H])C1([H])[H])=O)=O)OC([H])([H])[H])OC([H])([H])[H] |
| InChi Key | VABYUUZNAVQNPG-BQYQJAHWSA-N |
| InChi Code | InChI=1S/C17H19NO5/c1-21-13-10-12(11-14(22-2)17(13)23-3)7-8-16(20)18-9-5-4-6-15(18)19/h4,6-8,10-11H,5,9H2,1-3H3/b8-7+ |
| Chemical Name | 1-[(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoyl]-2,3-dihydropyridin-6-one |
| Synonyms | Piperlongumine; Piplartine |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | reactive oxygen species (ROS); TrxR1; CRM1; PI3K/Akt/mTOR |
| ln Vitro | Piperlongumine is a known ROS inducer that has the potential to cause the death of pancreatic cancer cells in culture[1] Platelet aggregation is prevented by piperlongumine, a thromboxane A(2) receptor antagonist. [2] In addition to promoting autophagy and mediating cancer cell death, piperlongumine inhibits Akt/mTOR signalling.[3] |
| ln Vivo | Piperlongumine (50 mg/kg i.p.) causes tumor cell in vivo growth inhibition without significantly altering biochemical, hematological, or histopathological parameters. [4] |
| Cell Assay | Various PL concentrations are incubated with MCF-7 and 786-O cells for 48 hours. CellTiter Blue assay is used to analyze cell proliferation. With the help of the Microsoft Excel add-in XLift, effective doses (ED) are calculated. |
| Animal Protocol |
Mice transplanted with sarcoma 180 tumors ~50 mg/kg i.p. |
| References |
[1]. Toxicol Rep . 2014:1:309-318. [2]. Eur J Pharmacol . 2007 Sep 10;570(1-3):38-42. [3]. Nat Prod Res . 2014;28(22):2040-3. [4]. J Appl Toxicol . 2008 Jul;28(5):599-607. [5]. Cancer Lett . 2016 May 28;375(1):114-126. [6]. Chem Biol Interact . 2015 Jul 25:237:66-72. [7]. Apoptosis . 2014 Jul;19(7):1148-64. |
| Additional Infomation |
Piplartine is a member of cinnamamides and a dicarboximide. Piperlongumine has been reported in Piper arborescens, Piper puberulum, and other organisms with data available. See also: Long Pepper (part of). |
Solubility Data
| Solubility (In Vitro) |
DMSO: 63~100 mg/mL (198.5~315.1 mM) Ethanol: ~63 mg/mL (~198.5 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: ≥ 2.08 mg/mL (6.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 4: 2% DMSO+40% PEG 300+2% Tween 80+ddH2O: 5mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1512 mL | 15.7560 mL | 31.5119 mL | |
| 5 mM | 0.6302 mL | 3.1512 mL | 6.3024 mL | |
| 10 mM | 0.3151 mL | 1.5756 mL | 3.1512 mL |