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Constrained Analogues of Procaine as Novel Small Molecule Inhibitors of DNA Methyltransferase-1.

Journal of medicinal chemistry 2008 Mar 18; In press

Link to PubMed abstract

Castellano S S, Kuck D D, Sala M M, Novellino E E, Lyko F F, Sbardella G G

gsbardella@unisa.it.

Constrained analogues of procaine were synthesized, and their inhibiting activity against DNMT1 was tested. Among them, the most potent compound, derivative 3b, was also able to induce a recognizable demethylation of chromosomal satellite repeats in HL60 human myeloid leukemia cells and thus represents a lead compound for the development of a novel class of non-nucleoside DNMT1 inhibitors.

Keywords: Procaine DNA Methyltransferase-1 DNMT1 leukemia