This review article tries to be an update of 2008 Pungitore’s review. Again, this paper tries to summarize the investigation about natural products, synthetic and non-nucleoside compounds with the ability to inhibit enzymes that play a crucial role in DNA metabolism such as replication, transcription, retro-transcription, recombination, and chromosome segregation during mitosis. The focus is placed on DNA polymerases, topoisomerases and reverse transcriptase inhibitors because most of the literature emphasized on their inhibitory activity. A great diversity of chemical compounds encompassing triterpenes, flavonoids, chromones, lipids, iridoids, phytosterols, coumarins, anthracyclines, quinones, protoberberines, tannins, lignans, acetogenins, benzimidazoles and other natural products, produced by different species of organisms, have inhibitory activities against enzymes related to DNA metabolism allowing these enzymes to arise as important molecular targets for cancer and AIDS research.
Keywords: DNA polymerases, inhibitors, natural products, non-nucleoside, reverse transcriptase, topoisomerases.