20069-09-4

Basic information

• Product Name: PIPERLONGUMINE
• Synonyms: PIPERLONGUMIN;PIPERLONGUMINE;PIPLARTINE;5,6-DIHYDRO-1-[1-OXO-3-3,4,5-TRIMETHOXYPHENYL-TRANS-2-PROPENYL]-21H-PYRIDINONE;piperlongumine from long pepper;5,6-Dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]pyridin-2(1H)-one;5,6-dihydro-1-[1-oxo-3-(3,4,5-triMethoxyphenyl)-allyl]-2(1H)-pyridinone;(E)-5,6-Dihydro-1-[1-oxo-3-(3,4,5-triMethoxyphenyl)-2-propenyl]-2(1H)-pyridinone
• CAS NO: 20069-09-4
• Molecular Formula: C₁₇H₁₉NO₅
• Molecular Weight: 317.34
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 20069-09-4.mol
• Article Data: 10

Chemical Properties

• Melting Point: 124°C
• Boiling Point: 475.6°Cat760mmHg
• Flash Point: 241.4°C
• Appearance: white to beige/
• Density: 1.223g/cm³
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥5mg/mL at warmed to 60°C
• PKA: -1.88±0.20(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: PIPERLONGUMINE(CAS DataBase Reference)
• NIST Chemistry Reference: PIPERLONGUMINE(20069-09-4)
• EPA Substance Registry System: PIPERLONGUMINE(20069-09-4)

Safety Data

• WGK Germany: 3
• RTECS: UU7785850
• Hazardous Substances Data: 20069-09-4(Hazardous Substances Data)

Usage

Description

A piperidinone alkaloid present in Piper longum, the structure has been shown to be N-(3:4:5-trimethoxycinnamoyl)-Lls-piperidin-2-one. In the plant, the base occurs mainly in the roots.

Uses

Different sources of media describe the Uses of 20069-09-4 differently. You can refer to the following data:
1. Piperlongumine has been used to study the regulation of protein regulator of cytokinesis 1 (PRC1) expression. It has also been used to investigate its anti-tumor effects on human melanoma cells in vitro.
2. Piperlongumine (PL), a new alkaloid abundantly present in Piper longum fruits strongly inhibited platelet cell aggregation. It may have anti-cancer properties. It selectively targets and kills cancer cells but leaving normal cells unharmed.
3. anti-asthma, antibronchitis

General Description

Piperlongumine is an alkaloid, which is extracted from Piper longum Linn. It exhibits anti-atherosclerotic, anxiolytic, antidiabetic, antidepressant, antibacterial, anti-platelet, aggregation, anxiolytic and anti-inflammatory properties. Piperlongumine prevents the production of tumor necrosis factor-α and interleukin-6. It blocks the activation of nuclear factor-κB (NF-κB) against proinflammatory responses. Piperlongumine inhibits plaque formation and inhibits vascular smooth muscle cell migration. It is used to treat cough, respiratory infections and stomach-ache.

Biochem/physiol Actions

Piperlongumine selectively kills cancer cells regardless of p53 status without harming normal cells. It binds to and inihbits proteins known to regulate oxidative stress, in particular, Glutathione S-transferase pi 1 (GSTP1). It increases the level of reactive oxygen species (ROS) and apoptotic cell death in cancer cells with little effect on either rapidly or slowly dividing primary normal cells. Piperlongumine showed significant antitumour effects in a variety of mouse tumour models and inhibited growth of spontaneously formed malignant breast tumours and their associated metastases.

References

Chatterjee, Dutta., Tetrahedron, 23, 1769 (1967)

InChI:InChI=1/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+

Upstream product

• 6052-73-9 5,6-dihydro-2(1H)-pyridinone 
• 89652-63-1 (E)-3-(3,4,5-trimethoxyphenyl)acrylic anhydride 
• 21651-12-7 (E)-2,4-pentadienoic acid 
• 86-81-7 3,4,5-trimethoxy-benzaldehyde 
• 1878-29-1 ethyl (E)-3-(3,4,5-trimethoxyphenyl)acrylate 
• 20329-98-0 (E)-3,4,5-trimethoxy-cinnamic acid 
• 1415686-28-0 N-(but-3-en-1-yl)prop-2-enamide 
• 82017-78-5 1-[(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoyl]piperidin-2-one 
• 10263-19-1 (E)-3-(3,4,5-trimethoxyphenyl)acryloyl chloride 
• 675-20-7 piperidin-2-one 
• 85908-96-9 2-oxopiperidine-1-carboxylic acid tert-butyl ester 
• 358732-56-6 N-(tert-butyloxycarbonyl)-3-(phenylthio)piperidine-2-one 
• 128372-89-4 6-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 104261-03-2 3-(phenylthio)piperidin-2-one 

Downstream Products

• 2466-36-6 1-(3-(3,4,5-trimethoxyphenyl)propanoyl)piperidin-2-one 
• 1337905-67-5 [-(3-(5-methoxy-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)propanoyl)-5,6-dihydropyridin-2(1H)-one] 
• 1415686-51-9 (E)-3-(hydroxy(2-nitrophenyl)methyl)-1-(3-(3,4,5-trimethoxyphenyl)acryloyl)-5,6-dihydropyridin-2(1H)-one 
• 30687-11-7 (E)-N-(2-hydroxyethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide 
• 970-85-4 (E)-1-(piperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 
• 1878-29-1 ethyl (E)-3-(3,4,5-trimethoxyphenyl)acrylate 
• 20329-96-8 methyl 3,4,5-trimethoxycinnamate 

Relevant articles and documents

Design and synthesis of benzylidenecyclohexenones as TrxR inhibitors displaying high anticancer activity and inducing ROS, apoptosis, and autophagy

Oxidative therapy, a strategy that specifically increases reactive oxygen species (ROS) levels in tumor cells by disrupting the redox homeostasis has gained increasing interest. The antitumor effects of the natural product piperlongumine (PL) appear to result from its ability to increase intracellular ROS levels via inhibition of antioxidative thioredoxin reductase (TrxR). Twenty-seven benzylidenecyclohexenone-based PL analogues (2a-v and 15a-e) were designed, synthesized and evaluated for their pharmacological properties. Most of the compounds exhibited potent antiproliferative activities against five human cancer cell lines, especially against breast tumor cells. One of the most promising analogueues 2c showed 12-fold higher inhibitory activity against the thioredoxin reductase (TrxR) than PL and surpressed the expression of TrxR1 protein in breast cancer cells and inhibited TrxR enzymatic activity. In addition, 2c increased ROS levels and resulted in marked apoptosis by regulating apoptosis-related proteins expressed in the breast cancer cells. Compound 2c also triggered the formation of autophagosomes and autolysosomes by promoting the expression of LC3-II and Beclin-1 and diminishing the expression of LC3-I and p62 proteins. Finally, 2c displayed low acute toxicity and good inhibitory potency to tumors in mice. Overall, 2c is a promising anti-breast cancer candidate warranting further investigation.

Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation

Selective clearance of senescent cells (SCs) has emerged as a potential therapeutic approach for age-related diseases, as well as chemotherapy- and radiotherapy-induced adverse effects. Through a cell-based phenotypic screening approach, we recently identified piperlongumine (PL), a dietary natural product, as a novel senolytic agent, referring to small molecules that can selectively kill SCs over normal or non-senescent cells. In an effort to establish the structure-senolytic activity relationships of PL analogues, we performed a series of structural modifications on the trimethoxyphenyl and the α,β-unsaturated δ-valerolactam rings of PL. We show that modifications on the trimethoxyphenyl ring are well tolerated, while the Michael acceptor on the lactam ring is critical for the senolytic activity. Replacing the endocyclic C2–C3 olefin with an exocyclic methylene at C2 render PL analogues 47–49 with increased senolytic activity. These α-methylene containing analogues are also more potent than PL in inducing ROS production in WI-38 SCs. Similar to PL, 47–49 reduce the protein levels of oxidation resistance 1 (OXR1), an important oxidative stress response protein that regulates the expression of a variety of antioxidant enzymes, in cells. This study represents a useful starting point toward the discovery of senolytic agents for therapeutic uses.

Pipelongumine and its derivatives and producing method thereof

The present invention relates to piperlongumine, a derivative thereof, and a synthesizing method thereof. The piperlongumine and the derivatives thereof are synthesized by making a variety of amides/lactams react with a variety of acid chlorides of 3,4,5-trimethoxycinnamic acid. In addition, anti-inflammatory effect is tested in RAW264.7 macrophage induced by LPS with respect to the compounds. The piperlongumine of the compounds shows maximum inhibition activity (91.3%) and has cytotoxicity. A compound 3 having alpha, beta-unsaturated butyrolactam does not show cytotoxicity, and has a significant inhibition effect of 64.8%. An amide/lactam region connected to an alpha, beta-unsaturated cinnamoyl group having the chain length of at least three carbons exhibits a strong anti-inflammatory activity without cytotoxicity.