Overview of the therapeutic potential of piplartine (piperlongumine)

Bezerra, Daniel P.; Pessoa, Cláudia; Moraes, Manoel Odoríco de; Saker-Neto, Nicolau; Silveira, Edilberto R.; Costa-Lotufo, Letı́cia V.

doi:10.1016/j.ejps.2012.12.003

Cited by 284 publications

(254 citation statements)

References 55 publications

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“…16 It is described as possessing antifungal properties, 17 cytotoxicity toward several cancer cell lines, 18,19 and trypanocidal effects, 20 as well as other biological activities. 21 Furthermore, piperlongumine selectively induces cell death in cancer cells but does not reduce viability in normal cells. 22 This natural compound also demonstrates an interesting capacity to reduce angiogenesis and inhibit the formation of blood vessels in tumor xenografts in mice.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration

Valli¹,

Altei²,

Santos³

et al. 2017

J. Braz. Chem. Soc.

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Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for discovering antimetastatic agents because this process is fundamental to metastasis. Piperlongumine, selected from cell-based assay screening of NuBBE Database, inhibited the migration of MDA-MB-231 breast cancer cells with an EC 50 of 3.0 ± 1.0 µM by the Boyden chamber assay. A series of five analogous compounds based on the structure of piperlongumine were designed, synthesized and evaluated in cell migration and cytotoxicity assays. The analogue designed by molecular simplification ((E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide) was the most active of the series, with an EC 50 of 1.5 ± 1 µM. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4. Keywords: piperlongumine, piplartine, piperamide, cytotoxicity, cell migration inhibition IntroductionMetastasis is the process by which undifferentiated cancer cells migrate to other parts of the body.1,2 Suppression of metastasis is an urgent need in cancer treatment, as most existing drugs only inhibit cell proliferation.3 Traditionally, chemotherapy is based on cytotoxic therapeutic agents that inhibit proliferation and cause cell death. However, the strategy of inhibiting cell migration has recently gained considerable interest. 4 Several compounds that inhibit the process of metastasis have been described to date. 5,6 Paclitaxel, which was originally discovered as an antimitotic agent that disrupts the cell cycle in cancer cells by stabilizing microtubules, exhibits marked and selective inhibition of tumor cell migration. 7As extensively reviewed elsewhere, biodiversity in nature has provided unique chemical scaffolds that have been used as templates for medicinal chemistry and drug discovery. [8][9][10][11][12][13] The availability of natural compound libraries is of significant importance for integrating natural products and medicinal chemistry, especially for the identification of new bioactive agents and the rational design of compounds in drug discovery.14 Within this context, we selected the natural product piperlongumine (1), also known as piplartine, from cell-based assay screening of NuBBE Database (NuBBE DB ) 15 and evaluated its ability to inhibit Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration J. Braz. Chem. Soc. 476 cancer cell migration using biological and target-based experiments.Piperlongumine (1, Figure 1) is an alkamide isolated from several species of Piper (Piperaceae). 16 It is described as possessing antifungal properties, 17 cytotoxicity toward several cancer cell lines, 18,19 and trypanocidal effects, 20 as well as other biological activities. 21 Furthermore, piperlongumine selectively induces cell death in cancer cells but does not reduce viability in normal cells. 22This ...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration

Valli¹,

Altei²,

Santos³

et al. 2017

J. Braz. Chem. Soc.

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“…Piperlongumine (also known as piplartine, 1, Figure 1) is an alkaloid isolated from a number of Piper plant species, including the long pepper plant Piper longum L. It has a large number of reported uses in traditional medicine, and has demonstrated cytotoxic and antitumour activity [2].…”

Section: Introductionmentioning

confidence: 99%

Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents

Meegan

Nathwani

Twamley

et al. 2017

European Journal of Medicinal Chemistry

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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 depolymerised 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.3

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“…Many species of the genus Piper, the most representative of the Piperaceae, have been used for centuries in traditional folk medicine and in culinary (Parmar et al 1997, Oliveira et al 2013, Bezerra et al 2013, Picard et al 2014. Piperine was the first amide isolated from P. nigrum (black pepper) and is responsible for the characteristic pungency of this plant (Ahmad et al 2012, Qiu et al KELVIN S.E.…”

Section: Introductionmentioning

confidence: 99%

“…LÓPEZ et al 2014). Many bioactive amides from Piper species were already chemically and pharmacologically investigated (Parmar et al 1998, Ahmad et al 2012, Bezerra et al 2013.…”

Section: Introductionmentioning

confidence: 99%

Local Anesthetic Activity from Extracts, Fractions and Pure Compounds from the Roots of Ottonia anisum Spreng. (Piperaceae)

López

Marques

Moreira

et al. 2016

An. Acad. Bras. Ciênc.

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Piperaceae species can be found worldwide in tropical and subtropical areas and many of them have been used for centuries in traditional folk medicine and in culinary. In Brazil, species of Piperaceae are commonly used in some communities as local anesthetic and analgesic. Countrified communities have known some species of the genus Ottonia as "anestesia" and it is a common habit of chewing leaves and roots of Ottonia species to relief toothache. The purpose of this study is to report our findings on new molecules entities obtained from the roots of Ottonia anisum Spreng, in which local anesthetic activity (sensory blockage) is demonstrated for the first time in vivo guinea pig model. Phytochemical investigation led to the isolation of three amides (pipercallosidine, piperine and valeramide) and in an enriched mixture of seven amides (valeramide, 4,5-dihydropiperlonguminine, N-isobutil-6-piperonil-2-hexenamide, piperovatine, dihydropipercallosidine, pipercallosidine and pipercallpsine). Our findings demonstrated the anesthetic potential for the methanolic extract from roots, its n-hexane partition and amides from O. anisum and it is in agreement with ethnobotanical survey.

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Overview of the therapeutic potential of piplartine (piperlongumine)

Cited by 284 publications

References 55 publications

Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration

Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration

Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents

Local Anesthetic Activity from Extracts, Fractions and Pure Compounds from the Roots of Ottonia anisum Spreng. (Piperaceae)

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