Inhibited DNMT activities

The covalent trapping of the enzyme leads to a depletion of the cellular pool of DNMTs and subsequent DNA hypomethylation. This in turn results in activation with respect to the reactivation of silenced genes. Additionally, the covalently trapped DNMT may inhibit RNA and DNA polymerases, which leads to an inhibition of protein biosynthesis and DNA strand breaks. This may lead to apoptosis and hence cytotoxicity. Thus, it is not easy to dissect the reasons for the clinical efficacy of these inhibitors in terms of real epigenetic and plain cytotoxic effects [81]. 

Several studies have shown the ability of DNMT inhibitors to prevent cancer using different pathways [101-104]. Genistein demonstrated cancer chemopreventive activities in animal models [105]. It has been studied in different cancer cell lines and inhibition of cancer cell growth has been shown [106]. But several mechanisms, such as antihormonal effects, are discussed to explain this activity and the exact contribution of DNMT inhibition to in-vivo activity in cancer chemoprevention remains to be determined. 

Acetylenic functionalities, as in peyssonenynes A and B (57 and 58) from the red alga Peyssonnelia caulifera (Yanuca Island, Fiji), ° are rare for macroalgae, with only one previous report of lipid acetylenes, produced by the red alga Liagorafarinosa Both 57 and 58 showed similar activity in a DNA methyltransferase (DNMT-1) enzyme inhibition assay, with an IC5o=16 and 9pmoll respectively, but peyssopyrone (59), also from... 

Enzyme-Based Histone Deacetylase (HDAC) and DNA Methyltransferase (DNMT) Inhibition Data, and Cell-Based p21 Promoter Activity Data, for the Psammaplins (772). 

Alkaloids HDAC enzyme inhibition IC50 (nM) ceU-based fold induction activity AC50 (pM) max fold induction (22 MFI is produced at 0.5 pM) DNMT enzyme inhibition IC50 (nM) ... 

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