- Preparation of phenylethylbenzamide derivatives as modulators of DNMT3 activity
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DNA-methyltransferases (DNMTs) are a class of epigenetic enzymes that catalyze the transfer of a methyl moiety from the methyl donor S-adenosyl-l-methionine onto the C5 position of cytosine in DNA. This process is dysregulated in cancers and leads to the hypermethylation and silencing of tumor suppressor genes. The development of potent and selective inhibitors of DNMTs is of utmost importance for the discovery of new therapies for the treatment of cancer. We report herein the synthesis and DNMT inhibitory activity of 29 analogues derived from NSC 319745. The effect of selected compounds on the methylation level in the MDA-MB-231 human breast cancer cell line was evaluated using a luminometric methylation assay. Molecular docking studies have been conducted to propose a binding mode for this series.
- Kabro, Anzhelika,Lachance, Hugo,Marcoux-Archambault, Iris,Perrier, Valerie,Dore, Vicky,Gros, Christina,Masson, Veronique,Gregoire, Jean-Marc,Ausseil, Frederic,Cheishvili, David,Laulan, Nathalie Bibens,St-Pierre, Yves,Szyf, Moshe,Arimondo, Paola B.,Gagnon, Alexandre
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p. 1562 - 1570
(2013/12/04)
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- Synthesis and biological investigations of nitric oxide releasing nateglinide and meglitinide type II antidiabetic prodrugs: In-vivo antihyperglycemic activities and blood pressure lowering studies
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A new group of hybrid nitric oxide-releasing type II antidiabetic drugs possessing a 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (13 and 18), 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (14 and 19), or nitrooxyethyl (15 and 20) moiety attached to the car
- Kaur, Jatinder,Bhardwaj, Atul,Huang, Zhangjian,Narang, Deepak,Chen, Ting-Yueh,Plane, Frances,Knaus, Edward E.
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p. 7883 - 7891
(2012/11/07)
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- Receptor Binding Sites of Hypoglycemic Sulfonylureas and Related benzoic Acids
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The blood glucose level lowering activity of benzoic acid, such as p-benzoic acid (HB699, 2), is discussed in terms of binding at putative insulin-releasing receptor sites of pancreatic β cells.The hypoglycemic potencies fuond for synthetic analogues of 2 indicate that high hypoglycemic activity is only found when a carboxyl group or a group that is readily oxidized to carboxyl in vivo, such as methyl, is attached to the aromatic ring of the phenethyl group.It is proposed that this carboxyl group is able to bind at the same receptor site as the SO2NHCONH group of the sulfonylurea drugs, such as tolbutamide (3).The role of the benzamide group in 2 was attributed to protein binding.
- Brown, George R.,Foubister, Alan J.
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- Benzoic acids, their derivatives and process for preparing them
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Acyl-aminoalkyl-benzoic acid and derivates thereof show a blood sugar lowering effect upon oral administration and can be used as orally applicable hypoglycemiants.
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