The potential role of the 5,6-dihydropyridin-2(1<i>H</i>)-one unit of piperlongumine on the anticancer activity

Mu, Wen-Wen; Li, Peng-Xiao; Liu, Yue; Yang, Jie; Liu, Guoyun

doi:10.1039/d0ra08778e

Cited by 8 publications

(13 citation statements)

References 41 publications

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“…In particular, ROS can be triggered by chemotherapeutic agents containing Michael acceptor units, which can irreversibly inhibit TrxR through a Michael reaction and result in the covalent modification of proteins [31] . Our group′s work was exploiting ROS‐promoting signaling for designing curcumin‐, piperlongumin‐, and bischalcone‐inspired anticancer agents [32,33,34] …”

Section: Discussionmentioning

confidence: 99%

“…The target molecules were obtained through acylation reaction between cinnamoyl chloride and 1,3‐Dimethylbarbituric acid. Firstly, substituted benzaldehyde condensed with malonic acid in pyridine, and then the solid were recrystallized from ethanol to afford corresponding cinnamic acids (intermediate 2 ) as previously reported [33] . Second, the intermediate 3 was obtained from intermediate 2 (3 mmol) and oxalyl chloride (3 mmol) followed by reported procedure [33] .…”

Section: Methodsmentioning

confidence: 99%

“…Firstly, substituted benzaldehyde condensed with malonic acid in pyridine, and then the solid were recrystallized from ethanol to afford corresponding cinnamic acids (intermediate 2 ) as previously reported [33] . Second, the intermediate 3 was obtained from intermediate 2 (3 mmol) and oxalyl chloride (3 mmol) followed by reported procedure [33] . Lastly, the intermediate 3 was dissolved in anhydrous CH 2 Cl 2 (5.6 mL), then, the pyridine solution of 1,3‐Dimethylbarbituric acid (3 mmol) was slowly added.…”

Section: Methodsmentioning

confidence: 99%

“…After 4 h, formazan crystals were dissolved in DMSO. The absorbance of each well was measured by use of microplate spectrophotometer at 570 nm as reported previously [33] …”

Section: Methodsmentioning

confidence: 99%

“…HeLa cells (4×10 5 /well) were seeded in 6‐well plate and treated with 1c and the vehicle alone as a control for 22 h. Then, the cells were harvested, washed with PBS and lysed. Finally, the levels of GSH and GSSG were determined by using a GSH and GSSG Assay Kit [33] …”

Section: Methodsmentioning

confidence: 99%

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Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

Liu

et al. 2022

Chemistry & Biodiversity

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This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3‐dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta‐ of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho‐ and para‐substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…After 4 h, formazan crystals were dissolved in DMSO. The absorbance of each well was measured by use of microplate spectrophotometer at 570 nm as reported previously [33] …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

Liu

et al. 2022

Chemistry & Biodiversity

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Piperlongumine and its derivatives against cancer: A recent update and future prospective

Swain,

Sahoo

2024

Archiv der Pharmazie

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Piperlongumine, or piplartine (PL), is a bioactive alkaloid isolated from Piper longum L. and a potent phytoconstituent in Indian Ayurveda and traditional Chinese medicine with a lot of therapeutic benefits. Apart from all of its biological activities, it demonstrates multimodal anticancer activity by targeting various cancer‐associated pathways and being less toxic to normal cells. According to their structure–activity relationship (SAR), the trimethylphenyl ring (cinnamoyl core) and 5,6‐dihydropyridin‐2‐(1H)‐one (piperdine core) are responsible for the potent anticancer activity. However, it has poor intrinsic properties (low aqueous solubility, poor bioavailability, etc.). As a result, pharmaceutical researchers have been trying to optimise or modify the structure of PL to improve the drug‐likeness profiles. The present review selected 26 eligible research articles on PL derivatives published between 2012 and 2023, followed by the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) format. We have thoroughly summarised the anticancer potency, mode of action, SAR and drug chemistry of the proposed PL‐derivatives against different cancer cells. Overall, SAR analyses with respect to anticancer potency and drug‐ability revealed that substitution of methoxy to hydroxyl, attachment of ligustrazine and 4‐hydroxycoumarin heterocyclic rings in place of phenyl rings, and attachment of heterocyclic rings like indole at the C7‐C8 olefin position in native PL can help to improve anticancer activity, aqueous solubility, cell permeability, and bioavailability, making them potential leads. Hopefully, the large‐scale collection and critical drug‐chemistry analyses will be helpful to pharmaceutical and academic researchers in developing potential, less‐toxic and cost‐effective PL‐derivatives that can be used against different cancers.

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Stereoselective Synthesis of Biheterocycles Containing Indole and 5,6‐Dihydropyridin‐2(1H)‐one or α‐Methylene‐β‐butyrolactam Scaffolds

et al. 2022

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Dedicated to Professor Joan Bosch on the occasion of his 75th birthdayIndium-mediated allylation of N-tert-butanesulfinyl imines derived from indole-2 and 3-carbaldehydes 3 and 5 with allylic bromides 6, proceed with high diastereoselectivity. Homoallylic amide derivatives 13 and 14 are transformed into dihydropyridinones 15 and 16, upon successive desulfinylation, N-acylation with acryloyl chloride and ring-closing-metathesis. Desulfinylation of amine ester derivatives 17 and 18, obtained when ethyl 2-(bromomethyl)acrylate (6 b) is used as the allylating reagent, lead to the corresponding α-methylene-γbutyrolactams 19 and 20, in modest yields.

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The potential role of the 5,6-dihydropyridin-2(1H)-one unit of piperlongumine on the anticancer activity

Abstract: Piperlongumine (PL) could induce A549 cells apoptosis through ROS-mediated pathway and the 5,6-dihydropyridin-2-(1H)-one unit is crucial for its anticancer activity.

Cited by 8 publications

References 41 publications

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

Piperlongumine and its derivatives against cancer: A recent update and future prospective

Stereoselective Synthesis of Biheterocycles Containing Indole and 5,6‐Dihydropyridin‐2(1H)‐one or α‐Methylene‐β‐butyrolactam Scaffolds

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