Synthesis and Cytotoxicity of Substituted Ethyl 2‐Phenacyl‐3‐phenylpyrrole‐4‐carboxylates

Evans, Michael A.; Smith, Daniel C.; Holub, Justin M.; Argenti, Anthony; Hoff, Mafoloe; Dalglish, Gerard A.; Wilson, Donna; Taylor, Brett M.; Berkowitz, Joshua D.; Burnham, Bruce S.; Krumpe, Keith E.; Gupton, John T.; Scarlett, Tanya; Durham, Richard W.; Hall, Iris H.

doi:10.1002/ardp.200390018

Cited by 14 publications

(8 citation statements)

References 28 publications

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“…The substituted pyrroles, which were synthesized based on similarity to marine derived compounds [1,2], have previously been demonstrated to have significant growth inhibitory activity against a variety of human tumor cell lines, with antiproliferative effects evident at nanomolar concentrations in some human breast tumor cell lines [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03-14, a novel microtubule poison

Arthur

Gupton

Kellogg

et al. 2007

Biochemical Pharmacology

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JG-03-14, a substituted pyrrole that inhibits microtubule polymerization, was screened against MCF-7 (p53 wild type), MDA-MB 231 (p53 mutant), MCF-7/caspase 3 and MCF-7/ADR (multidrug resistant) breast tumor cell lines. Cell viability and growth inhibition were assessed by the crystal violet dye assay. Apoptosis was evaluated by the TUNEL assay, cell cycle distribution by flow cytometry, autophagy by acridine orange staining of vesicle formation, and senescence based on β-galactosidase staining and cell morphology. Our studies indicate that exposure to JG-03-14, at a concentration of 500 nM, induces time dependent cell death in the MCF-7 and MDA-MB 231 cell lines. In MCF-7 cells, a residual surviving cell population was found to be senescent; in contrast, there was no surviving senescent population in treated MDA-MB 231 cells. No proliferative recovery was detected over a period of 15 days post-treatment in either cell line. Both the TUNEL assay and FLOW cytometry indicated a relatively limited degree of apoptosis (< 10%) in response to drug treatment in MCF-7 cells with more extensive apoptosis (but < 20%) in MDA-MB231 cells; acidic vacuole formation indicative of autophagic cell death was relatively extensive in both MCF-7 and MDA-MB231 cells. In addition, JG-03-14 induced the formation of a large hyperdiploid cell population in MDA-MB231 cells. JG-03-14 also demonstrated pronounced anti-proliferative activity in MCF-7/caspase 3 cells and in the MCF-7/ADR cell line. The observation that JG-03-14 promotes autophagic cell death and also retains activity in tumor cells expressing the multidrug resistance pump indicates that novel microtubule poisons of the substituted pyrroles class may hold promise in the treatment of breast cancer.

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Section: Introductionmentioning

confidence: 99%

Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03-14, a novel microtubule poison

Arthur

Gupton

Kellogg

et al. 2007

Biochemical Pharmacology

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“…The regioselective synthesis of 2,3,4-trisubstituted pyrroles from chloroenals has recently been reported by Gupton, et. al [1][2][3][4]32,33]. The convergent synthesis generates acceptable yields through the final condensation, however with the aid of the XT reactor (Mettler-Toledo AutoChem), up to six derivatives were easily prepared under a dry, inert atmosphere and constant temperature.…”

Section: Chemistrymentioning

confidence: 99%

“…The resulting white solid was filtered and washed with cold THF. [1]. Obtained from 2-azido-4'-chloroacetophenone (22g) as a white solid (81%); mp = 232-233 …”

Section: O)mentioning

confidence: 99%

“…2,4-Disubstituted brominated pyrroles, which are brominated at positions 3 and 5 along with 2,3,4-trisubstituted pyrroles have demonstrated potent cytotoxic activity in vitro against a variety of murine and human suspended and solid tumor models [1][2][3][4]. Also, pentasubstituted pyrroles have proven to be potent hypocholesterolemic agents through the inhibition of HMG-CoA reductase activity, a key enzyme in the de novo synthesis of cholesterol [5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

et al. 2004

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-A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDLcholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole.

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“…Pyrroles, the third heteroaryls in this introduction, exhibited numerous biological activities, including anticoagulant , antimicrobial , human tumor models , antiviral , and anticonvulsant activities . Based on the aforementioned observation, current investigation of this work was on the synthesis of new pyrrole and 1,4‐dihydropyridine derivatives and evaluated for pharmacological activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Pharmacological Evaluation of Some New Chromeno[3,4‐c]pyrrole‐3,4‐dione‐based N‐Heterocycles as Antimicrobial Agents

Azab

Elkanzi

2016

Journal of Heterocyclic Chem

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The reaction of 2‐oxo‐2H‐chromene‐3‐carboxamide (1) with carbon disulfide afforded 1‐mercaptopyrrolo[3,4‐c]chromene‐3,4‐dione (3). The latter compound was utilized as versatile building block for new azole systems via incorporating in a series of manipulations including cyclocondensation reactions. The structure of the newly synthesized compounds has been confirmed by IR, 1H NMR, 13C NMR, mass spectral, and elemental analysis. Furthermore, some selected compounds were screened in vitro for their antimicrobial activities. The results declared that most of the synthesized compounds have high antimicrobial activity.

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Synthesis and Cytotoxicity of Substituted Ethyl 2‐Phenacyl‐3‐phenylpyrrole‐4‐carboxylates

Cited by 14 publications

References 28 publications

Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03-14, a novel microtubule poison

Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03-14, a novel microtubule poison

Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

Synthesis and Pharmacological Evaluation of Some New Chromeno[3,4‐c]pyrrole‐3,4‐dione‐based N‐Heterocycles as Antimicrobial Agents

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