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| HAL: hal-00680950, version 1 |
| PubMed: 22170584 |
| DOI: 10.1002/cbic.201100522 |
| Detailed view |  Export this paper |
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| ChemBioChem 13, (1) (2012) 157-65 |
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| Rapid synthesis of new DNMT inhibitors derivatives of procainamide. |
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| Ludovic HalbyChristine Champion |
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| (2012-01-02) |
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| DNA methyltransferases (DNMTs) are responsible for DNA methylation, an epigenetic modification involved in gene regulation. Families of conjugates of procainamide, an inhibitor of DNMT1, were conceived and produced by rapid synthetic pathways. Six compounds resulted in potent inhibitors of the murine catalytic Dnmt3A/3L complex and of human DNMT1, at least 50 times greater than that of the parent compounds. The inhibitors showed selectivity for C5 DNA methyltransferases. The cytotoxicity of the inhibitors was validated on two tumour cell lines (DU145 and HCT116) and correlated with the DNMT inhibitory potency. The inhibition potency of procainamide conjugated to phthalimide through alkyl linkers depended on the length of the linker; the dodecane linker was the best. |
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| 1: | Laboratoire des biomolécules (LBM) |
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Université Pierre et Marie Curie (UPMC) - Paris VI – CNRS : UMR7203 – Ecole normale supérieure de Paris - ENS Paris |
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| 2: | Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB) |
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CNRS : UMR7613 – Université Pierre et Marie Curie (UPMC) - Paris VI |
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| 3: | CNRS, Paris, France (UMR 7613) |
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Université Pierre et Marie Curie (UPMC) - Paris VI |
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| 4: | Laboratoire de Chimie de la Matière Condensée de Paris (site Paris VI) (LCMCP (site Paris VI)) |
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CNRS : UMR7574 – Collège de France – Université Pierre et Marie Curie (UPMC) - Paris VI – Ecole Nationale Supérieure de Chimie de Paris |
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| Subject | : | Chemical Sciences/Organic chemistry |
| hal-00680950, version 1 | |
| http://hal.archives-ouvertes.fr/hal-00680950 | |
| oai:hal.archives-ouvertes.fr:hal-00680950 | |
| From: Nicolas Perron | |
| Submitted on: Tuesday, 20 March 2012 14:49:07 | |
| Updated on: Tuesday, 20 March 2012 14:49:07 | |
