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Design and synthesis of N-benzoyl amino acid derivatives as DNA methylation inhibitors.
- Source :
- Chemical Biology & Drug Design; Nov2016, Vol. 88 Issue 5, p664-676, 13p
- Publication Year :
- 2016
-
Abstract
- The inhibition of human DNA Methyl Transferases ( DNMT) is a novel promising approach to address the epigenetic dysregulation of gene expression in different diseases. Inspired by the validated virtual screening hit NSC137546, a series of N-benzoyl amino acid analogues was synthesized and obtained compounds were assessed for their ability to inhibit DNMT-dependent DNA methylation in vitro. The biological screening allowed the definition of a set of preliminary structure-activity relationships and the identification of compounds promising for further development. Among the synthesized compounds, L-glutamic acid derivatives 22, 23, and 24 showed the highest ability to prevent DNA methylation in a total cell lysate. Compound 22 inhibited DNMT1 and DNMT3A activity in a concentration-dependent manner in the micromolar range. In addition, compound 22 proved to be stable in human serum and it was thus selected as a starting point for further biological studies. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17470277
- Volume :
- 88
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Chemical Biology & Drug Design
- Publication Type :
- Academic Journal
- Accession number :
- 118584254
- Full Text :
- https://doi.org/10.1111/cbdd.12794