Aciclovir structure

Aciclovir is a member of a group of nucleoside derivatives termed acyclonucleosides, in that there is an incomplete sugar ring. The structural relationship to 2 -deoxyguanosine should be very clear. Aciclovir is converted into its monophosphate by the viral enzyme thymidine kinase - some viruses also possess enzymes that facilitate their replication in the host cell. The viral enzyme turns out to be much more effective than that of the host cell, and conversion is, therefore, mainly in infected cells. The monophosphate is subsequently converted into the triphosphate hy the host cell enzymes. Aciclovir triphosphate inhibits viral DNA polymerase, much more so than it does the host enzyme, and so terminates DNA replication. 

Common Name Aciclovir valinate Valaciclovir Valacyclovir Structural Formula ... 

The structure of ganciclovir (Fig. 23.17) is closely related to that of aciclovir. Ganciclovir has the equivalent of 3 and 5 hydroxyl groups within its structure and thus, unlike adclovir, it can become incorporated into DNA and thus has a broader spectrum of activity. The absence of a 5-membered ribose or deoxyribose sugar to maintain the stmctural rigidity of the sugar-phosphate backbone of the newly synthesized nucleic add means that its stmcture... 

Penciclovir (Fig. 23.17) is closely related to ganciclovir in structure and has the same mechanism of action. Penciclovir has similar activity to aciclovir against herpes simplex infection. Its safety is similar to that of aciclovir due to its lack of effect on DNA synthesis in uninfected cells. A closer structural similarity to deoxyguanosine makes penciclovir a superior substrate in comparison to aciclovir for viral thymidine kinase, resulting in an enhancement of phosphorylation. This is offset by reduced activity of penciclovir triphosphate as an inhibitor of DNA synthesis. It has poor oral bioavailability and is used in the form of a cream (1% w/w) to treat labial herpes. Famciclovir (Fig. 23.17) is a prodmg of penciclovir which has good oral bioavailability (73%) and is deacetylated and oxidised (aldehyde oxidase) in the liver to penciclovir. The toxicity of famciclovir is low. It is administered three times a day by mouth, whereas treatment of herpes with aciclovir by the oral route requires five daily doses. 

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