Synthesis of new troglitazone derivatives: Anti-proliferative activity in breast cancer cell lines and preliminary toxicological study

Salamone, Stéphane; Colin, Christelle; Grillier-Vuissoz, Isabelle; Kuntz, Sandra; Mazerbourg, Sabine; Flament, Stéphane; Martin, Hélène; Richert, Lysiane; Chapleur, Yves; Boisbrun, Michel

doi:10.1016/j.ejmech.2012.02.044

Cited by 60 publications

(46 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…48 The identity and purity of this compound were verified by proton nuclear magnetic resonance and elemental analysis. D2-TGZ was dissolved in Dimethyl sulfoxide (DMSO).…”

Section: Cell Lines and Reagentsmentioning

confidence: 99%

Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions

et al. 2016

Self Cite

View full text Add to dashboard Cite

We have previously shown that D2-Troglitazone (D2-TGZ) displayed anticancer effects on breast cancer cell lines grown in low serum conditions (1% fetal calf serum (FCS)). The present study was performed in order to characterize the effects of D2-TGZ in high serum containing medium and to determine if starvation could influence the response of breast cancer cells to this compound, keeping in mind the potential interest for breast cancer therapy. We observed that in high serum conditions (10% FCS), a 48 h treatment with D2-TGZ induced a decrease in cell numbers in MDA-MB-231 and MCF-7 breast cancer cell lines. The IC 50 values were higher than in low serum conditions. Furthermore, in contrast to our previous results obtained in 1% FCS conditions, we observed that in 10% FCS-containing medium, MCF-7 cells were more sensitive to D2-TGZ than MDA-MB-231 cells. D2-TGZ also induced endoplasmic reticulum (ER) stress mainly in MDA-MB-231 cells. Besides, in high serum conditions, D2-TGZ induced a G 0 /G 1 cell cycle arrest, an inhibition of BrdU incorporation and a reduced level of cyclin D1. We observed a limited cleavage of PARP and a limited proportion of cells in sub-G 1 phase. Thus, in high serum conditions, D2-TGZ displayed cytostatic effects rather than apoptosis as previously reported in 1% FCS-containing medium. Our results are in accordance with studies suggesting that serum starvation could potentiate the action of diverse anti-cancer agents.

show abstract

“…48 The identity and purity of this compound were verified by proton nuclear magnetic resonance and elemental analysis. D2-TGZ was dissolved in Dimethyl sulfoxide (DMSO).…”

Section: Cell Lines and Reagentsmentioning

confidence: 99%

Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Most of D2-TGZ-derivatives were functionalized on the terminal hydroxyl group of the chromane moiety, and showed a stronger activity on breast cancer cell viability [57]. Some of them had good antiproliferative effects in breast cancer cells and low toxicity in human hepatocytes [58]. D2-TGZ and D2-CGZ inhibited prostate cancer cells proliferation more strongly than their parent compounds, in PPARγexpressing PC-3 and PPARγ-deficient LNCaP cells [28].…”

Section: Er Stress Inductionmentioning

confidence: 99%

Antineoplastic Effects of PPAR? Agonists, with a Special Focus on Thyroid Cancer

Ferrari¹,

Materazzi²,

Baldini³

et al. 2016

CMC

View full text Add to dashboard Cite

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

show abstract

“…IR spectra (KBr disc) were recorded on Shimadzu FT-IR 8400S infrared spectrophotometer. NMR spectra were recorded on a Varian Mercury VX 300 spectrometer ( 1 H: 300, 13 C: 75 MHz) using TMS as an internal standard and on JOEL (Eclipse) 400 ( 1 H: 400, 13 C: 100 MHz). Mass spectra were measured on a Shimadzu GCMS-QP2010 Plus spectrometer (EI, 70 eV).…”

Section: Methodsmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11][12][13][14] Previously, we reported promising antitumor properties of a variety of 5-arylidene thiazolidinone derivatives Ia-c ( Fig. 1) exhibiting considerable cytotoxic activity against colon HCT116 cancer cell lines compared with Doxorubicin (reference standard, IC 50 =0.00686 mM).…”

mentioning

confidence: 99%

Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2-(4-Oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles

Hanna

George

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

2-(5-Arylidene-4-oxo-3-phenyl-thiazolidin-2-ylidene)-3-oxo-propionitriles 4a-j were prepared via condensation of aromatic aldehydes with 4-thiazolidinones 3a, b. The latter was obtained via electrophilic attack of phenylisothiocyanate on 3-oxo-propionitriles 1a, b followed by reaction with chloroacetyl chloride under basic condition. Additionally, 2-(5-heteroalicyclic methylene) analogues 5a-h were prepared via Mannich reaction of the appropriate secondary amines and formaldehyde with 4-thiazolidinones 3a, b. Many of the synthesized compounds exhibited promising antitumor properties against colon HCT116 and breast T47D cell lines. 3D-Pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis were combined to explain the observed antitumor properties.Key words thiazolidinone; quantitative structure-activity relationship; antitumor activity; 3-oxo-propionitrile; HCT116; T47D Cancer ranks second in diseases leading to mortality, following only cardiovascular diseases. One-quarter of all deaths in the United States are caused by cancer.1) Out of the many cancer diseases, breast cancer is the most prevalent cancer in women and represents the second highest leading cause of cancer death in this population after lung cancer.2) Colorectal cancer is the third most common cancer in both men and women, 91% of cases are diagnosed in individuals 50 years of age and older. 1) Chemotherapy is widely used to treat and control cell growth and limit the spread of cancer cells to other sites. Although, there is a success with certain forms of cancer, drug therapy has only limited impact against the three major killers: carcinoma of lung, breast and colorectal system. Therefore, there is a need to develop novel antitumor agents to treat and combat this disease.Several promising antitumor agents containing thiazolidine and thiazolidinone scaffolds have been identified to have a broad range of anticancer activities.3-14) Previously, we reported promising antitumor properties of a variety of 5-arylidene thiazolidinone derivatives Ia-c (Fig. 1) exhibiting considerable cytotoxic activity against colon HCT116 cancer cell lines compared with Doxorubicin (reference standard, IC 50 =0.00686 mM).15) In continuation of these previous findings and in order to optimize novel antitumor active agents possessing the same thiazolidinone core, it is intended in the present work to perform some modifications in the adopted structures via inserting heteroalicyclic amines (morpholinyl or piperidinyl functions, 4a-j) instead of the aromatic amines Ia-c due to their hydrophilic properties. Moreover, a series of heteroalicyclic methylene containing compounds 5a-h will be also prepared replacing the arylidene moiety of Ia-c (Fig. 1). Additionally, many morpholine and piperidine containing compounds were known as anticancer active agents that exerted their actions via inhibition of different targets such as phosphatidylinositol 3-kinases (PI3Ks) and histone deacetylase (HDAC). [16][17][18][19][20] Moreover, the piperidine deriva...

show abstract

Synthesis of new troglitazone derivatives: Anti-proliferative activity in breast cancer cell lines and preliminary toxicological study

Cited by 60 publications

References 40 publications

Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions

Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions

Antineoplastic Effects of PPAR? Agonists, with a Special Focus on Thyroid Cancer

Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2-(4-Oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles

Contact Info

Product

Resources

About