Design, Synthesis and Pharmacological Evaluation of Novel Piperlongumine derivatives as Potential Antiplatelet Aggregation Candidate

Wang, Yujun; Wang, Jie; Li, Jiaming; Zhang, Yanchun; Huang, Weijun; Zuo, Jian; Liu, Huicai; Xie, Di; Zhu, Panhu

doi:10.1111/cbdd.12714

Cited by 10 publications

(3 citation statements)

References 14 publications

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“…Piplartine ( 1 ) is an alkamide commonly found in long pepper ( Piper longum L.). Previous reports indicated piplartine exhibited a wide range of pharmacological activities, including anti-diabetic, anti-ulcer, anti-platelet aggregation, anti-atherosclerotic, anti-depressant, anti-bacterial and anti-fungal properties [ 11 , 12 , 13 , 14 ]. Moreover, this compound possesses a highly selective and effective antitumor property, which protects against various types of tumors [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

et al. 2018

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Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.

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Section: Introductionmentioning

confidence: 99%

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

et al. 2018

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“…The Piperlongumine (PL) was originally isolated from fruits of black pepper (Piper nigrum Linn) and long pepper ( Piper longum L.) ( Zhu et al, 2021 ). Cumulative evidence has suggested that PL and its derivatives elicit a broad spectrum of pharmacological activities, including anti-inflammatory ( Sant'Ana et al, 2020 ), neuroprotective ( Bezerra et al, 2013 ; Jung et al, 2013 ; Carreiro et al, 2014 ; Wiemann et al, 2017 ), antioxidant ( Li et al, 2019 ), anti-cancer ( Piska et al, 2018 ; Tripathi and Biswal, 2020 ; Sun et al, 2021 ), antiplatelet aggregation ( Wang et al, 2016 ), anti-diabetes ( Rao et al, 2012 ) and other biological activities. In 2018, Go et al reported PL treatment has been shown to regulate age-related cognitive decline in age correlates and hippocampal dysfunction in elderly mice ( Go et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

The protective effect of PL 1-3 on D-galactose-induced aging mice

Li,

Ma,

Wang

et al. 2024

Front. Pharmacol.

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The aging population has become an issue that cannot be ignored, and research on aging is receiving increasing attention. PL 1-3 possesses diverse pharmacological properties including anti-oxidative stress, inhibits inflammatory responses and anti-apoptosis. This study showed that PL 1-3 could protect mice, especially the brain, against the aging caused by D-galactose (D-gal). D-gal could cause oxidative stress, inflammation, apoptosis and tissue pathological injury and so on in aging mice. The treatment of PL 1-3 could increase the anti-oxidative stress ability in the serum, liver, kidney and brain of aging mice, via increasing the total antioxidant capacity and the levels of anti-oxidative defense enzymes (superoxide dismutase, glutathione peroxidase, and catalase), and reducing the end product of lipid peroxidation (malondialdehyde). In the brain, in addition to the enhanced anti-oxidative stress via upregulating the level of the nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, PL 1-3 could improve the dysfunction of the cholinergic system via reducing the active of acetylcholinesterase so as to increase the level of acetylcholine, increase the anti-inflammatory and anti-apoptosis activities via downregulating the expressions of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and pro-apoptosis proteins (Bcl-2 associated X protein and Caspase-3) in the D-gal-induced aging mice, to enhance the anti-aging ability via upregulating the expression of sirtuin 1 and downregulating the expressions of p53, p21, and p16. Besides, PL 1-3 could reverse the liver, kidney and spleen damages induced by D-gal in aging mice. These results suggested that PL 1-3 may be developed as an anti-aging drug for the prevention and intervention of age-related diseases.

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“…Piperlongumine ( 1 , Figure ) is an alkaloid isolated from the root of Piper longum L, of which trans -piperlongumine is the main natural stereoisomer . Piperlongumine displays various pharmacological activities, such as anticancer, antiplatelet aggregation, anti-inflammatory, antifungal, and antidepression. − Piperlongumine inhibits the proliferation and metastasis of cancer cells in various ways. It induces the production of high levels of ROS, with little influence of ROS in normal cells. ,, Additionally, it is also able to induce cancer cell cycle arrest. − Mechanistic studies showed that piperlongumine binds to glutathione (GSH) in cancer cells, leading to an increase in the level of ROS in cancer cells, and that ROS could form more active N-oxide (RNOS) with NO to inhibit cancer.…”

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confidence: 99%

Discovery of Cytotoxic Nitric Oxide-Releasing Piperlongumine Derivatives Targeting Wnt/β-Catenin in Colon Cancer Cells

Zou,

He,

Tan

et al. 2024

J. Nat. Prod.

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Piperlongumine (1) increases reactive oxygen species (ROS) levels and induces apoptosis in cancer cells through various pathways. Nitric oxide (NO) donors have demonstrated potent anticancer activities with exogenous NO being oxidized by ROS in the tumor microenvironment to form highly reactive Noxides (RNOS). This amplifies oxidative stress cascade reactions, ultimately inducing cancer cell apoptosis. To exploit this synergy, a series of NO-releasing piperlongumine derivatives (2−5) were designed and synthesized. These compounds were expected to release NO in cancer cells, simultaneously generating piperlongumine derivative fragments to enhance the anticancer effects. Compound 6, structurally similar to compounds 2−5 but not releasing NO, served as a control. Among these derivatives, compound 5 exhibited the most potent antiproliferative activity against HCT-116 cells and efficiently released NO in this cell line. Further investigation revealed that compound 5 inhibited colon cancer cell proliferation by modulating β-catenin expression, which is a pivotal protein in the Wnt/β-catenin signaling pathway. These findings highlight compound 5 as a promising candidate for colon cancer treatment targeting the Wnt/β-catenin pathway.

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Design, Synthesis and Pharmacological Evaluation of Novel Piperlongumine derivatives as Potential Antiplatelet Aggregation Candidate

Cited by 10 publications

References 14 publications

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

The protective effect of PL 1-3 on D-galactose-induced aging mice

Discovery of Cytotoxic Nitric Oxide-Releasing Piperlongumine Derivatives Targeting Wnt/β-Catenin in Colon Cancer Cells

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