1415152-85-0Relevant academic research and scientific papers
Activity-based protein profiling reveals GSTO1 as the covalent target of piperlongumine and a promising target for combination therapy for cancer
Li, Li,Zhao, Yue,Cao, Ran,Li, Lin,Cai, Gaihong,Li, Jiaojiao,Qi, Xiangbing,Chen, She,Zhang, Zhiyuan
supporting information, p. 4407 - 4410 (2019/04/26)
Through systematic target identification for piperlongumine, a cancer-selective killing molecule, we identified GSTO1 as its major covalent target for cancer cell death induction. We also reveal that GSTO1 inhibition is a promising combination strategy with other anti-cancer agents by drug combination screening in which piperlongumine exhibits broad-spectrum synergistic effects with a large proportion of the tested anti-cancer agents, especially with PI3K/Akt/mTOR pathway inhibitors.
Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation
Liu, Xingui,Wang, Yingying,Zhang, Xuan,Gao, Zhengya,Zhang, Suping,Shi, Peizhong,Zhang, Xin,Song, Lin,Hendrickson, Howard,Zhou, Daohong,Zheng, Guangrong
, p. 3925 - 3938 (2018/06/19)
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.
Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents
Meegan, Mary J.,Nathwani, Seema,Twamley, Brendan,Zisterer, Daniela M.,O'Boyle, Niamh M.
, p. 453 - 463 (2016/10/04)
Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerized when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, showing potent effects in human breast carcinoma MCF-7?cells whilst being relatively non-toxic to non-tumorigenic MCF-10a cells. These?compounds will be further developed as potential clinical candidates for the treatment of breast cancer.
Horner-Wadsworth-Emmons approach to piperlongumine analogues with potent anti-cancer activity
Han, Li-Chen,Stanley, Paul A.,Wood, Paul J.,Sharma, Pallavi,Kuruppu, Anchala I.,Bradshaw, Tracey D.,Moses, John E.
, p. 7585 - 7593 (2016/08/16)
Natural products with anti-cancer activity play a vital role in lead and target discovery. We report here the synthesis and biological evaluation of the plant-derived alkaloid, piperlongumine and analogues. Using a Horner-Wadsworth-Emmons coupling approach, a selection of piperlongumine-like compounds were prepared in good overall yield from a novel phosphonoacetamide reagent. A number of the compounds displayed potent anti-cancer activity against colorectal (HCT 116) and ovarian (IGROV-1) carcinoma cell lines, via a mechanism of action which may involve ROS generation. Contrary to previous reports, no selective action in cancer cell (MRC-5) was observed for piperlongumine analogues.
Compounds, Compositions, and Methods for Cancer Therapy
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Paragraph 0125; 0143, (2014/02/16)
Compounds including various oligomers of piperlongumine and/or piperlongumine analogues as well as certain piperlongumine analogues that exhibit improved toxicity to cancer cells are disclosed. Also provided are compositions that comprise the compounds, methods of making compositions comprising the compounds, methods of making the compounds, and the use of compounds in methods for treating cancer.
