| Epigenetic changes consist of DNA methylation, histone modification, micro RNA and genome imprinting. DNA methylation of the CpG islands is one of the main methods of epigenetic inactivation of genes and aberrant methylations at promoter regions of tumor suppressor genes can alter gene expression and play an important role in cancer development. DNA methyltransferase I (Dnmt1) is the enzyme responsible for maintaining methylation patterns during cell division and it is overexpressed in many cancers. Thus, Dnmt1 is a promising therapeutic target for development of novel anticancer agents and epigenetic modulators. We have developed two promising class of lead candidates, compounds 5-hydroxy-2-(4-hydroxyphenethyl)-3-oxo-N-pentyl-4-(4-(trifluoromethyl)phenyl)isoindoline-1-carboxamide 47, 2-(2-(1H-indol-3-yl)ethyl)-5-hydroxy-3-oxo-N-pentyl-4-(4-(trifluoromethyl)phenyl)isoindoline- 1-carboxamide 51 and 1-(4-isopropylphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole 96, as potential leads compounds that can be optimized for pharmaceutical applications.. |
