The present review is focused on the description of synthesis and antiviral activities of both acyclic and carbocyclic nucleoside phosphonates, endowed with an antiviral potential. Despite the outstanding results in antiviral therapy of acyclovir and azidothymidine, a major drawback concerning the use of nucleoside analogues (NA) is the retention of their stability following triphosphorylation within the host cell. The instability of the phosphate forms of NA has been, at least partially, overcome by the introduction of phosphate groups in the molecular structure. This approach gives rise to two main classes of compounds endowed with ascertained or potential antiviral activity, such as acyclic nucleoside phosphonates (ANP) and phosphonated carbocyclic nucleosides (PCN). Regarding ANP, a higher affinity for HIV reverse transcriptase (RT), with respect to NA, and the potent inhibition of HIV and hepatitis B virus (HBV) have been reported for some of them. Regarding PCN, some phosphonated cyclopropyl and cyclopentyl carbanucleosides, characterized by the presence of one or more phosphonic groups and by replacement of the endocyclic oxygen atom with a methylene group, showed to be good inhibitors of HBV and HIV infection. Another class of PCN is represented by phosphonated N,O-nucleosides (PCOAN). PCOAN encompass homo phosphonated-, phosphonated- and truncated phosphonated-N,O-nucleosides. Some PCOAN have been shown to directly inhibit RT activity of both murine and human retroviruses and to block HTLV-1 infection in vitro. The flexibility of the phosphonated NA structure suggests the possibility to develop new analogues endowed with antiviral activity towards a broad range of DNA or RNA viruses.
|Titolo:||Phosphonated Nucleoside Analogues as Antiviral Agents|
|Data di pubblicazione:||2015|
|Appare nelle tipologie:||2.1 Contributo in volume (Capitolo o Saggio)|