1415686-59-7

Upstream product

• 616-45-5 2-pyrrolidinon 
• 10263-19-1 (E)-3-(3,4,5-trimethoxyphenyl)acryloyl chloride 
• 20329-98-0 (E)-3,4,5-trimethoxy-cinnamic acid 

Relevant academic research and scientific papers

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells.

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.

Synthesis and biological evaluation of piperlongumine derivatives as potent anti-inflammatory agents

Piperlongumine (PL) and its derivatives were synthesized by the direct reaction between acid chloride of 3,4,5-trimethoxycinnamic acid and various amides/lactams. Later their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. Of the piperlogs prepared in this study, the maximum (91%) inhibitory activity was observed with PL (IC50 = 3 μM) but showed cytotoxicity whereas compound 3 (IC50 = 6 μM) which possess α,β-unsaturated γ-butyrolactam moiety offered good level (65%) of activity with no cytotoxicity. This study revealed that amide/lactam moiety connected to cinnamoyl group with minimum 3 carbon chain length and α,β-unsaturation is fruitful to show potent anti-inflammatory activity.

Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)

As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC50 of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells.