RESUMO
BACKGROUND: Over the last few years DNA methylation and its involvement in diseases such as cancer has become of great interest for applied research. Since reversal of aberrant DNA methylation may influence the behavior of tumors, the methylation of DNA CpG sites is a potential target for the development of inhibitors for use in cancer treatment. OBJECTIVE/METHODS: We briefly review the structural and mechanistic features of DNA methylation, including a structural analysis of the three main human DNA methyltransferases and some (pre)clinical results. RESULTS/CONCLUSION: Despite side effects, data obtained to date still support the vision that DNA-methylation, possibly associated with the use of histone deacetylases (HDACs) and/or artificial transcription factors (ATFs), is a promising target for improving anticancer therapy in the 21st century.
Assuntos
Antineoplásicos/farmacologia , Metilação de DNA/efeitos dos fármacos , DNA/metabolismo , Neoplasias/tratamento farmacológico , DNA/genética , Metilases de Modificação do DNA/química , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , HumanosRESUMO
Several new pyrazolo[4,3-c]quinolin-3-one ribonucleosides (5a-g) and their corresponding heterocycle moieties (3a-g) were synthesized and evaluated against vaccinia virus (VV) and herpes simplex virus type 1 (HSV-1). The derivatives 3c and 3d showed modest inhibitory activity against vaccinia virus reaching 70% at a concentration of 100 microM. All heterocyclic compounds (3a-f) showed a modest inhibition against HSV-1, reaching the maximal inhibitory effect around 20-30%. The antiviral effects of most of the pyrazolo[4,3-c]quinolin-3-one ribonucleosides (5a-f) on VV and HSV were not impressive.