Antiproliferative activity of some 1,4-dimethylcarbazoles on cells that express estrogen receptors: part I

Caruso, Anna; Chimento, Adele; El‐Kashef, Hussein; Lancelot, Jean‐Charles; Panno, Antonella; Pezzi, Vincenzo; Saturnino, Carmela; Sinicropi, Maria Stefania; Sirianni, Rosa; Rault, Syl­vain

doi:10.3109/14756366.2011.603132

Cited by 35 publications

(29 citation statements)

References 24 publications

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“…The organic layer was dried over anhydrous MgSO 4 , filtered and the solvent removed by evaporation. The resulting residue was purified by silica gel column chromatography in petroleum ether/ethyl acetate (1:9) to give a white/yellow solid in 67 % yield ( 2 a – g ) …”

Section: Methodsmentioning

confidence: 99%

“…The resulting residue was purified by silica gel column chromatography in petroleum ether/ethyl acetate (1:9) to give aw hite/ yellow solid in 67 %yield (2a-g). [16,49,63] General method for the synthesis of compounds 3a-g:1 -[2-(Dimethylamino)ethyl]piperazine (l.35 mmol) and Na 2 CO 3 (2.7 mmol) were dissolved in DMF (10 mL). As olution of N-bromoalkyl-substituted carbazole (2a-g,1 .35 mmol) in DMF (10 mL) was added at room temperature.…”

Section: Docking Simulationsmentioning

confidence: 99%

“…Some derivatives have shown interesting pharmaceutical properties, interfering with DNA‐dependent enzymes, such as topoisomerases I/II and telomerase, along with other targets such as cyclin‐dependent kinases and estrogen receptors. For these reasons, they occupy an important position as antitumor tools in preclinical and clinical trials …”

Section: Introductionmentioning

confidence: 99%

“…For these reasons, they occupy an important positiona sa ntitumor tools in preclinical and clinical trials. [7][8][9][10][11][12][13] Of particular interesti st he interaction with DNA or its metabolizing enzymes that induce programmedc ell death, namely apoptosis. [14][15][16][17][18] Several carbazole analogues structurally derived from ellipticine, an alkaloid from Ochrosia elliptica Chemotherapyi su sed for the treatment of all stages of breast cancer,i ncluding the metastatic stage of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

et al. 2018

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Chemotherapy is used for the treatment of all stages of breast cancer, including the metastatic stage of the disease. Treatment regimens are generally tailored for each patient′s particular situation. However, chemotherapeutic agents are the leading cause of serious drug‐related adverse effects; moreover, drug resistance often occurs. In this study, we designed and synthesized a new series of N‐alkylcarbazoles derived from ellipticine, an alkaloid with a carbazole skeleton initially used in the treatment of metastatic breast cancer and later dismissed because of poor aqueous solubility and severe side effects. After evaluating the binding modes of our class of newly synthesized compounds with human topoisomerase II (hTopo II), we performed hTopo II decatenation assays, identifying compound 4 f (2‐(4‐((3‐chloro‐9H‐carbazol‐9‐yl)pentyl)piperazin‐1‐yl)‐N,N,N‐trimethylethanammonium iodide) as a good inhibitor. Moreover, 4 f and 4 g (2‐(4‐((3‐chloro‐9H‐carbazol‐9‐yl)hexyl)piperazin‐1‐yl)‐N,N,N‐trimethylethanammonium iodide) showed a good anti‐proliferative activity toward breast cancer cells, causing apoptosis by activation of the caspase pathway. Interestingly, the activity of these two compounds on triple‐negative MDA‐MB‐231 cells, which tend to be highly metastatic and aggressive, is strictly connected to the observed inhibition of hTopo II.

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Section: Methodsmentioning

confidence: 99%

Section: Docking Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

et al. 2018

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“…Carbazoles display a wide range of biological activities, making them attractive compounds to synthetic and medicinal chemists . Carbazole and its derivatives are important type of nitrogen‐containing heterocyclic compounds that are widespread in nature.…”

Section: Introductionmentioning

confidence: 99%

A Green Synthesis of 2‐Amino‐4‐(9H‐carbazole‐3‐yl)thiophene‐3‐carbonitriles by a Step‐wise and One‐pot Three‐component Gewald Reaction

Avula

Vallela

Anireddy

et al. 2017

Journal of Heterocyclic Chem

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An eco‐friendly method has been developed for the synthesis of 2‐amino‐4‐(9H‐carbazole‐3‐yl)thiophene‐3‐carbonitriles from preliminary carbazole (1) through an intermediate of 2‐(1‐(9H‐carbazole‐3‐yl)ethylidene)malononitriles using the Knoevenagel condensation followed by the Gewald reaction. On the other hand, the target compounds could also be prepared in a one‐pot three‐component manner by treating equimolar quantities of 1‐(9H‐carbazole‐3‐yl)ethanone (3), malononitrile, and elemental sulfur. The merits of this preparation are mild reaction conditions. The Gewald reaction is executed with inorganic base NaHCO3 (H2O) in tetrahydrofuran, easy work‐up procedure with good yields.

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Novel Gold and Silver Carbene Complexes Exert Antitumor Effects Triggering the Reactive Oxygen Species Dependent Intrinsic Apoptotic Pathway

et al. 2017

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Cisplatin and other platinum-based drugs are well-known valid anticancer drugs. However, during chemotherapy, the presence of numerous side effects and the onset of frequent phenomena of resistance has pushed many research groups to devise new metal-based compounds holding improved anticancer properties and fewer undesired effects. Amongst the variety of synthesized compounds, significant antiproliferative effects have been obtained by employing organometallic compounds, particularly those based on silver and gold. With this in mind, we synthesized four compounds, two silver complexes and two gold complexes, with good inhibitory effects on the in vitro proliferation of breast and ovarian cancer-cell models. The antitumor activity of the most active compound, that is, AuL4, was found to be ninefold higher than that of cisplatin, and this compound induced dramatic morphological changes in HeLa cells. AuL4 induced PARP-1 cleavage, caspases 3/7 and 9 activation, mitochondria disruption, cytochrome c release in cancer-cell cytoplasm, and the intracellular production of reactive oxygen species. Thus, AuL4 treatment caused cancer-cell death by the intrinsic apoptotic pathway, whereas no cytotoxic effects were recorded upon treating non-tumor cell lines. The reported outcomes may be an important contribution to the expanding knowledge of medicinal bio-organometallic chemistry and enlarge the available anticancer toolbox, offering improved features, such as higher activity and/or selectivity, and opening the way to new discoveries and applications.

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Antiproliferative activity of some 1,4-dimethylcarbazoles on cells that express estrogen receptors: part I

Cited by 35 publications

References 24 publications

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

A Green Synthesis of 2‐Amino‐4‐(9H‐carbazole‐3‐yl)thiophene‐3‐carbonitriles by a Step‐wise and One‐pot Three‐component Gewald Reaction

Novel Gold and Silver Carbene Complexes Exert Antitumor Effects Triggering the Reactive Oxygen Species Dependent Intrinsic Apoptotic Pathway

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