DNA methyltransferases (DNMTs) are responsible for DNA methylation, an 
epigenetic modification involved in gene regulation. Families of conjugates of 
procainamide, an inhibitor of DNMT1, were conceived and produced by rapid 
synthetic pathways. Six compounds resulted in potent inhibitors of the murine 
catalytic Dnmt3A/3L complex and of human DNMT1, at least 50 times greater than 
that of the parent compounds. The inhibitors showed selectivity for C5 DNA 
methyltransferases. The cytotoxicity of the inhibitors was validated on two 
tumour cell lines (DU145 and HCT116) and correlated with the DNMT inhibitory 
potency. The inhibition potency of procainamide conjugated to phthalimide 
through alkyl linkers depended on the length of the linker; the dodecane linker 
was the best.