Heterocycles in Medicine 177Antiviral drugs
Many antiviral agents are modifi ed (often quite simply) nucleosides or fairly closely related structures, for example
ribavirin. These generally work by disrupting the synthesis of viral DNA following incorporation, in competition with
natural nucleosides, at an early stage. Non-nucleoside compounds, such as delavirdine and saquinavir, act by binding
close to the active site of an enzyme, altering its conformation and thereby deactivating it.
Anticancer drugs
Anticancer drugs generally act by disrupting the growth of cells and therefore oppose the excessive and abnormal
growth that is the basis of cancer pathology. They are often referred to as cytotoxic or antimetabolites. One of several
mechanisms can be operative: disrupting the synthesis of DNA either by N-alkylating one of the bases (adenine, gua-
nine, cytosine or thymine) or by incorporation of a modifi ed base or nucleoside by competition with the natural bases
for the DNA-synthesising enzymes. Alkylating agents are usually simple chemical ‘reagents’ or their precursors, an
example of the latter being temozolomide, a prodrug, which breaks down when hydrolysed in vivo to give the powerful
alkylating agent, methyl diazonium cation. Possibly the resemblance of temozolomide to a nucleic acid base allows it
to come into close contact with its target.