Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity.
Chemical manipulations performed on the histone H3 lysine 9 methyltransferases (G9a/GLP) inhibitor BIX-01294 afforded novel desmethoxyquinazolines able to inhibit the DNA methyltransferase DNMT3A at low micromolar levels without any significant inhibition of DNMT1 and G9a. In KG-1 cells such compoun...
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doaj-281a01d650e04497b3316ad698b79eb42020-11-25T01:58:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9694110.1371/journal.pone.0096941Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity.Dante RotiliDomenico TarantinoBiagina MarroccoChristina GrosVéronique MassonValérie PoughonFréderic AusseilYanqi ChangDonatella LabellaSandro CosconatiSalvatore Di MaroEttore NovellinoMichael SchnekenburgerCindy GrandjenetteCeline BouvyMarc DiederichXiaodong ChengPaola B ArimondoAntonello MaiChemical manipulations performed on the histone H3 lysine 9 methyltransferases (G9a/GLP) inhibitor BIX-01294 afforded novel desmethoxyquinazolines able to inhibit the DNA methyltransferase DNMT3A at low micromolar levels without any significant inhibition of DNMT1 and G9a. In KG-1 cells such compounds, when tested at sub-toxic doses, induced the luciferase re-expression in a stable construct controlled by a cytomegalovirus (CMV) promoter silenced by methylation (CMV-luc assay). Finally, in human lymphoma U-937 and RAJI cells, the N-(1-benzylpiperidin-4-yl)-2-(4-phenylpiperazin-1-yl)quinazolin-4-amine induced the highest proliferation arrest and cell death induction starting from 10 µM, in agreement with its DNMT3A inhibitory potency.http://europepmc.org/articles/PMC4014597?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dante Rotili Domenico Tarantino Biagina Marrocco Christina Gros Véronique Masson Valérie Poughon Fréderic Ausseil Yanqi Chang Donatella Labella Sandro Cosconati Salvatore Di Maro Ettore Novellino Michael Schnekenburger Cindy Grandjenette Celine Bouvy Marc Diederich Xiaodong Cheng Paola B Arimondo Antonello Mai |
spellingShingle |
Dante Rotili Domenico Tarantino Biagina Marrocco Christina Gros Véronique Masson Valérie Poughon Fréderic Ausseil Yanqi Chang Donatella Labella Sandro Cosconati Salvatore Di Maro Ettore Novellino Michael Schnekenburger Cindy Grandjenette Celine Bouvy Marc Diederich Xiaodong Cheng Paola B Arimondo Antonello Mai Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity. PLoS ONE |
author_facet |
Dante Rotili Domenico Tarantino Biagina Marrocco Christina Gros Véronique Masson Valérie Poughon Fréderic Ausseil Yanqi Chang Donatella Labella Sandro Cosconati Salvatore Di Maro Ettore Novellino Michael Schnekenburger Cindy Grandjenette Celine Bouvy Marc Diederich Xiaodong Cheng Paola B Arimondo Antonello Mai |
author_sort |
Dante Rotili |
title |
Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity. |
title_short |
Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity. |
title_full |
Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity. |
title_fullStr |
Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity. |
title_full_unstemmed |
Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity. |
title_sort |
properly substituted analogues of bix-01294 lose inhibition of g9a histone methyltransferase and gain selective anti-dna methyltransferase 3a activity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Chemical manipulations performed on the histone H3 lysine 9 methyltransferases (G9a/GLP) inhibitor BIX-01294 afforded novel desmethoxyquinazolines able to inhibit the DNA methyltransferase DNMT3A at low micromolar levels without any significant inhibition of DNMT1 and G9a. In KG-1 cells such compounds, when tested at sub-toxic doses, induced the luciferase re-expression in a stable construct controlled by a cytomegalovirus (CMV) promoter silenced by methylation (CMV-luc assay). Finally, in human lymphoma U-937 and RAJI cells, the N-(1-benzylpiperidin-4-yl)-2-(4-phenylpiperazin-1-yl)quinazolin-4-amine induced the highest proliferation arrest and cell death induction starting from 10 µM, in agreement with its DNMT3A inhibitory potency. |
url |
http://europepmc.org/articles/PMC4014597?pdf=render |
work_keys_str_mv |
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