A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness

Barcelos, Rosimeire Coura; Pelizzaro-Rocha, Karin Juliane; Pastre, Julio Cezar; Dias, Marina Pereira; Ferreira-Halder, Carmen Veríssima; Pilli, Ronaldo A.

doi:10.1016/j.ejmech.2014.09.085

Cited by 21 publications

(13 citation statements)

References 78 publications

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“…In particular, inhibition of chronic inflammation, which precedes or accompanies tumor development, has recently come to light as an attractive option. Racemic GTN, a styryl lactone found in its R configuration in plants of the genus Goniothalamus, Annonaceae, has in vitro antiproliferative activity in human tumor cell lines via activation of apoptosis (18)(19)(20)23,38). GTN also presents general anti-inflammatory effects, without side effects (as seen with aspirin, for example) in the therapeutic doses (20,22,39).…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Vendramini–Costa

Francescone

Posocco

et al. 2016

CARCIN

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The tumor microenvironment offers multiple targets for cancer therapy, including pro-tumorigenic inflammation. Natural compounds represent an enormous source of new anti-inflammatory and anticancer agents. We previously showed that the styryl lactone goniothalamin (GTN) has promising antiproliferative and anti-inflammatory activities. Because inflammation is a major driver of colorectal cancer (CRC), we therefore evaluated the therapeutic and preventive potentials of GTN in colitis, colitis-associated cancer (CAC) and spontaneous CRC. First, in a simplistic model of inflammation in vitro, GTN was able to inhibit cytokine production in bone marrow-derived macrophages induced by lipopolysaccharide. Next, in dextran sulfate sodium (DSS) induced-colitis model, mice treated with GTN displayed restored tissue architecture, increased cell proliferation in the colonic crypts and reduced epithelial damage. Moreover, colon tissue from GTN-treated mice had significantly less expression of the inflammatory genes interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), S100A9, interleukin 23A (IL-23A), IL-22 and IL-17A. In the azoxymethane/DSS model of CAC, GTN reduced tumor multiplicity, load and size. Additionally, GTN suppressed production of IL-6, IL-17 and TNF-α in tumor tissue, as well as abrogated stromal immune cell activation and nuclear translocation of NF-κB. Finally, in a tamoxifen inducible model of sporadic CRC, GTN-treated mice had significantly fewer tumors and decreased levels of IL-17A, IL-6, S100A9 and TNF-α protein within the tumors. These results suggest that GTN possesses anti-inflammatory and antitumor activities and represents a preventive and therapeutic agent modulating the inflammatory environment in the colon during colitis as well as CAC and CRC development.

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Section: Discussionmentioning

confidence: 99%

Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Vendramini–Costa

Francescone

Posocco

et al. 2016

CARCIN

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“…25,26 To a solution of acid chloride (1.0 equiv.) in CH 2 Cl 2 were added triethylamine (TEA, 3.0 equiv.)…”

Section: Synthesis Of Pl and Its Analogues (mentioning

confidence: 99%

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

et al. 2015

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The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells.

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“…However, Pilli and co-workers were able to demonstrate that acylation of aza-goniothalamin 1 yielded analogues such as compound 3 with significantly improved biological profiles (IC 50 = 11 µM, U251 cell line, Figure 1). Thus, a path for the generation of a new class of potential anticancer agents based on the aza-goniothalamin framework was determined [17,18].…”

Section: Introductionmentioning

confidence: 99%

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

Cogswell

Donald

Marquez

2020

Beilstein J. Org. Chem.

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A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness

Cited by 21 publications

References 78 publications

Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

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