didanosine brands

Molecular formula: C10H12N4O3

Didanosine (ddI) is metabolized intracellularly by a series of cellular enzymes to its active moiety, dideoxyadenosine triphosphate (ddATP), which inhibits the HIV reverse transcriptase enzyme competitively by competing with natural dATP. It also acts as a chain terminator by its incorporation into viral DNA as the lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. The complete mechanism(s) of antiviral activity of didanosine has not been fully elucidated. Following conversion to a pharmacologically active metabolite, didanosine apparently inhibits replication of retroviruses, including human immunodeficiency virus, by interfering with viral RNA directed DNA polymerase (reverse transcriptase). The drug, there exerts a virustatic effect against retroviruses by acting as a reverse transcriptase inhibitor. Like other nucleoside reverse transcriptase inhibitors (eg, abacavir, lamivudine, stavudine, zalcitabine, zidovudine) and other nucleoside antiviral agents (eg, acyclovir, ganciclovir, ribavirin), the antiviral activity of didanosine appears to depend on intracellular conversion of the drug to a 5'-triphosphate metabolite; thus, dideoxyadenosine-5'-triphosphate and not unchanged didanosine appears to be the pharmacologically active form of the drug. Substantial differences exist in the rates at which human cells phosphorylate various nucleoside analog antiviral agents and in the enzymatic pathways involved. Dideoxyadenosine-5'-triphosphate can bind to inhibit some mammalian cellular DNA polymerases, particularly beta- and gamma-polymerases, in vitro. However, dideoxyadenosine-5'-triphosphate and other dideoxynucleoside triphosphate appear to have much greater affinity for viral RNA directed DNA polymerase than for mammalian DNA polymerases, particularly mammalian DNA alpha-polymerase, a DNA enzyme essential for cell division and cellular DNA repair. This differential sensitivity of mammalian and viral DNA polymerases to dideoxynucleotide triphosphates may account, in part, for some of the antiviral selectivity of these drugs in cells that can phosphorylate them. However, inhibition of beta- and gamma-polymerases by these drugs may account to some extent, for the toxic effects associated with didanosine and other dideoxynucelosides in humans.

Source: PubChem (NCBI) · compound 135398739