SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes

Bioorg Med Chem Lett. 2009 May 15;19(10):2747-51. doi: 10.1016/j.bmcl.2009.03.113. Epub 2009 Mar 28.


The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N(6)-amino moiety favors the inhibition of DNMT3b2 enzyme.

MeSH terms

  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • S-Adenosylhomocysteine / chemical synthesis*
  • S-Adenosylhomocysteine / chemistry
  • S-Adenosylhomocysteine / pharmacology
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • S-Adenosylhomocysteine
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA (cytosine-5-)-methyltransferase 3b2, human
  • DNMT1 protein, human