Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on PPARα

Ammazzalorso, Alessandra; D’Angelo, Alessandra; Giancristofaro, Antonella; Filippis, Barbara De; Matteo, Mauro Di; Fantacuzzi, Marialuigia; Giampietro, Letizia; Linciano, Pasquale; Maccallini, Cristina; Amoroso, Rosa

doi:10.1016/j.ejmech.2012.10.019

Cited by 23 publications

(17 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the search for novel PPARα ligands, we identified sulfonamide derivatives 1a–d (Figure ) showing a PPARα antagonistic profile in the micromolar range . These molecules also showed a PPARγ antagonism, whereas no PPARδ activity was observed .…”

Section: Introductionsupporting

confidence: 59%

“…In Figure is depicted a summary of SAR studies performed on our benzothiazole PPAR ligands; while carboxylic acids are PPARα agonists, benzenesulfonamide bioisosteres showed antagonistic properties. The introduction of substituents in para position of aromatic ring was tolerated, and the presence of amide groups resulted in compounds with better potency.…”

Section: Resultsmentioning

confidence: 73%

See 1 more Smart Citation

Cytotoxic effect of a family of peroxisome proliferator‐activated receptor antagonists in colorectal and pancreatic cancer cell lines

et al. 2017

Self Cite

View full text Add to dashboard Cite

Recent studies report an interesting role of peroxisome proliferator-activated receptor (PPAR) antagonists in different tumor models, being these compounds able to perturb metabolism and viability in cancer cells. In this work, the identification of a novel PPAR antagonist, showing inhibitory activity on PPARα and a weaker antagonism on PPARγ, is described. The activity of this compound and of a series of chemical analogues was investigated in selected tumor cell lines, expressing both PPARα and PPARγ. Data obtained show a dose-dependent cytotoxic effect of the novel PPAR antagonist in colorectal and pancreatic cancer models.

show abstract

Section: Introductionsupporting

confidence: 59%

Section: Resultsmentioning

confidence: 73%

Cytotoxic effect of a family of peroxisome proliferator‐activated receptor antagonists in colorectal and pancreatic cancer cell lines

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…The use of inhibitors of the PPAR pathway or a method preventing its activation could enhance the advantage of using cancer immunotherapy based on V9V2 T cells. Indeed, the repression of PPAR expression can be induced by TNF [24] or by a group of N-(methylsulfonyl)amides derived from PPAR agonist carboxylic acids with an antagonist behavior on PPAR [25]. Some kinases or their activators can also lead to specific inhibition of PPAR transcriptional activity, such as the MEK1 or AMP-activated protein kinase activators 5-aminoimidazole-4-carboxamide riboside [26,27].…”

Section: Resultsmentioning

confidence: 99%

The PPARα pathway in Vγ9Vδ2 T cell anergy

Poupot

Boissard

Bétous

et al. 2014

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

Phosphoantigens (PAgs) activate V9V2 T lymphocytes, inducing their potent and rapid response in vitro and in vivo. However, humans and nonhuman primates that receive repeated injections of PAgs progressively lose their V9V2 T cell response to them. To elucidate the molecular mechanisms of this in vivo desensitization, we analyzed the transcriptome of circulating V9V2 T cells from macaques injected with PAg. We showed that three PAg injections induced the activation of the PPAR pathway in V9V2 T cells. Thus, we analyzed the in vitro response of V9V2 T cells stimulated with a PPAR agonist. We demonstrated that in vitro PPAR pathway activation led to the inhibition of the BrHPP-induced activation and proliferation of human V9V2 T cells. Since the PPAR pathway is involved in the antigen-selective desensitization of human V9V2 T cells, the use of PPAR inhibitors could enhance cancer immunotherapy based on V9V2 T cells.

show abstract

“…AA452 is a N ‐acylsulfonamide derivative able to revert PPARα activation promoted by the GW7647 agonist at low micromolar concentrations . A time‐resolved fluorescence resonance energy‐transfer (TR‐FRET) assay shows that AA452 is a competitive PPARα antagonist . It has been tested in different tumor cell lines and has been shown to affect the viability of colorectal and pancreatic cancer cells .…”

Section: Ppar Antagonists and Cancermentioning

confidence: 99%

“…[78] At ime-resolved fluorescencer esonance energy-transfer (TR-FRET) assay shows that AA452 is a competitive PPARa antagonist. [79] It has been tested in different tumor cell lines and has been shown to affect the viability of colorectal and pancreatic cancerc ells. [80] In ar ecent study,t his compound has been tested in human glioblastoma (GB)p rimary cells, inducing strong effects on cell viability, proliferation, and migration related to the mevalonate pathway.I na ddition, AA452 is able to increaset he sensitivityo fG Bt og old standard radiationt herapy,o pening new possibilities to test this compound in preclinical studies.…”

Section: Ppara Antagonistsmentioning

confidence: 99%

The Anticancer Potential of Peroxisome Proliferator‐Activated Receptor Antagonists

et al. 2018

Self Cite

View full text Add to dashboard Cite

The effects on cancer-cell proliferation and differentiation mediated by peroxisome proliferator-activated receptors (PPARs) have been widely studied, and pleiotropic outcomes in different cancer models and under different experimental conditions have been obtained. Interestingly, few studies report and little preclinical evidence supports the potential antitumor activity of PPAR antagonists. This review focuses on recent findings on the antitumor in vitro and in vivo effects observed for compounds able to inhibit the three PPAR subtypes in different tumor models, providing a rationale for the use of PPAR antagonists in the treatment of tumors expressing the corresponding receptors.

show abstract

Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on PPARα

Cited by 23 publications

References 36 publications

Cytotoxic effect of a family of peroxisome proliferator‐activated receptor antagonists in colorectal and pancreatic cancer cell lines

Cytotoxic effect of a family of peroxisome proliferator‐activated receptor antagonists in colorectal and pancreatic cancer cell lines

The PPARα pathway in Vγ9Vδ2 T cell anergy

The Anticancer Potential of Peroxisome Proliferator‐Activated Receptor Antagonists

Contact Info

Product

Resources

About