Overview of piperlongumine analogues and their therapeutic potential

Zhu, Peng; Qian, Jianqiang; Xu, Zhongyuan; Meng, Chunyan; Zhu, Wuqiang; Ran, Fansheng; Zhang, Wei; Zhang, Yanan; Ling, Yong

doi:10.1016/j.ejmech.2021.113471

Cited by 44 publications

(24 citation statements)

References 147 publications

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“…Piperlongumine (PL) ( 12 ), a pyridone alkaloid, was first isolated and identified from Piper longum L. in 1967 . PL has been extensively investigated in subsequent research and has shown diverse bioactivities, including antiangiogenic, antidepressant, antidiabetic, neuroprotective, anti-inflammatory, and anticancer effects. , The antitumor activity of PL was reported to be partially associated with the two reactive α,β-unsaturated ketone moieties (Figure ). Recently, PL was shown to selectively induce the proteasomal degradation of OXR1 to inhibit senescent cells, where it could be combined with eight different E3 ligases. , In MOLT4 cancer cells, nine E3 ligases, including Keap1, were confirmed through an ABPP method using a PL-Alkyne probe, indicating that PL can be applied as a novel E3 ligase recruiter in PROTAC discovery.…”

Section: Np-inspired Targeted Protein Degradersmentioning

confidence: 99%

“…44 PL has been extensively investigated in subsequent research and has shown diverse bioactivities, including antiangiogenic, antidepressant, antidiabetic, neuroprotective, anti-inflammatory, and anticancer effects. 45,46 The antitumor activity of PL was reported to be partially associated with the two reactive α,β-unsaturated ketone moieties (Figure 4). 47 Recently, PL was shown to selectively induce the proteasomal degradation of OXR1 to inhibit senescent cells, where it could be combined with eight different E3 ligases.…”

Section: Np-inspired Targeted Protein Degradersmentioning

confidence: 99%

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Natural Product-Inspired Targeted Protein Degraders: Advances and Perspectives

Cai

et al. 2022

J. Med. Chem.

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Targeted protein degradation (TPD), a promising therapeutic strategy in drug discovery, has great potential to regulate the endogenous degradation of undruggable targets with small molecules. As vital resources that provide diverse structural templates for drug discovery, natural products (NPs) are a rising and robust arsenal for the development of therapeutic TPD. The first proof-of-concept study of proteolysis-targeting chimeras (PROTACs) was a natural polyketide ovalicin-derived degrader; since then, NPs have shown great potential to promote TPD technology. The use of NP-inspired targeted protein degraders has been confirmed to be a promising strategy to treat many human conditions, including cancer, inflammation, and nonalcoholic fatty liver disease. Nevertheless, the development of NP-inspired degraders is challenging, and the field is currently in its infancy. In this review, we summarize the bioactivities and mechanisms of NP-inspired degraders and discuss the associated challenges and future opportunities in this field.

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Section: Np-inspired Targeted Protein Degradersmentioning

confidence: 99%

Section: Np-inspired Targeted Protein Degradersmentioning

confidence: 99%

Natural Product-Inspired Targeted Protein Degraders: Advances and Perspectives

Cai

et al. 2022

J. Med. Chem.

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“…3.3.9. Piperlongumine Piperlongumine (Figure 4), an alkaloid found in long pepper (Piper longum), has been implicated in suppressing the growth of numerous cancer cells by pleiotropically modulating different oncogenic signaling pathways [263][264][265]. Makhov et al [125] studied the effects of piperlongumine on the 786-O RCC cell line, where it was shown to decrease cell viability and proliferation.…”

Section: Oxymatrinementioning

confidence: 99%

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

Bajalia

Azzouz

Chism

et al. 2022

Cancers

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Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.

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“…Piperlongumine (PL), a natural alkaloid found in Piper longum, contains 3,4,5-trimethoxycinnamoyl moiety and two α,β-unsaturated imide moieties acting as Michael acceptor sites. In recent years, PL has attracted considerable attention for anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Hepatoprotective Effects of Piperlongumine Derivative PL 1–3-Loaded Albumin Nanoparticles on Lipopolysaccharide/d-Galactosamine-Induced Acute Liver Injury in Mice

Guo

Liu

et al. 2022

Mol. Pharmaceutics

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In recent years, piperlongumine (PL) having specific cytotoxicity has attracted considerable attention for anticancer activity. Through structural modification, the active derivative PL 1−3 shows potential anti-inflammatory activity and low cytotoxicity, but its water solubility is low. Here, PL 1−3loaded bovine serum albumin nanoparticles (1−3 NPs) were prepared and characterized, which can improve the dissolution. 1− 3 NPs exhibited effective hepatoprotective effects on lipopolysaccharide/D-galactosamine-induced acute liver injury of mice, which was similar to liver injury in clinical settings. 1−3 NPs treatment can inhibit inflammation, oxidative stress, and apoptosis via the downregulation of NF-κB signaling pathways, the activation of Nrf2/HO-1 signaling pathways, and the inhibition of expression of Bax and caspase 3 proteins. The above results demonstrated that PL 1−3-loaded bovine serum albumin nanoparticles possessed potential value in intervention of inflammation-based liver injury.

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Overview of piperlongumine analogues and their therapeutic potential

Cited by 44 publications

References 147 publications

Natural Product-Inspired Targeted Protein Degraders: Advances and Perspectives

Natural Product-Inspired Targeted Protein Degraders: Advances and Perspectives

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

Evaluation of Hepatoprotective Effects of Piperlongumine Derivative PL 1–3-Loaded Albumin Nanoparticles on Lipopolysaccharide/d-Galactosamine-Induced Acute Liver Injury in Mice

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