Initial studies on the cellular pharmacology of 2′,3′-dideoxyinosine, an inhibitor of HIV infectivity

Effects of dideoxyinosine and dideoxycytidine on the intracellular phosphorylation of zidovudine in human mononuclear cells.

“…combination therapy, is regarded as being a major therapeutic strategy in the future treatment of HIV infection. It is known that the other major nucleoside analogues ddl and ddC must also be phosphorylated intracellularly in order to elicit antiretroviral activity [31][32][33][34]. Therefore, it is important to ascertain any possible interaction of either ddI or ddC with ZDV phosphorylation.…”

Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction.

“…Despite a vigorous quest for substances that could interact with and inhibit or inactivate a specific HIV protein and thus interfere with progression through the viral reproductive cycle, the only drugs found to be clinically useful thus far are compounds inhibiting the activity of reverse transcriptase (RT) in synthesizing viral DNA. 3'-Azido-3'-deoxythymidine (AZT) is widespread in clinical use (3,4), and the related nucleosides ,2',3'-dideoxycytidine (ddC) (5) and 2',3'-dideoxyinosine (ddI) (6), presently in clinical trials, show additional potential in reducing clinical symptoms of AIDS. The efficacy of such nucleosides is limited to new infections of susceptible cells, and virus production in previously infected cells continues unabated.…”

“…The efficacy of such nucleosides is limited to new infections of susceptible cells, and virus production in previously infected cells continues unabated. Also, severe toxicities of long-term treatments (5,7) and the occurrence of AZT-resistant mutants (8) Al of poly(rA)-(dT)10 (2 units/ml), 6.5 ,l of distilled H20, 0.5 ,l of 10% (vol/vol) Triton X-100, and 10 ,l of 100 nM [3H]dTTP (16.56 Ci/mmol; 1 Ci = 37 GBq). Samples were incubated for 30 min at 37°C and allowed to adsorb onto Whatman DE81 ion-exchange paper for 15 min.…”

Molecular Pharmacology of Nucleoside and Nucleotide HIV-1 Reverse Transcriptase Inhibitors

“…Didanosine is phosphorylated to didanosine-MP by cytosolic 5'-nucleotidase, which uses either inosine monophosphate (IMP) or guanosine monophosphate (GMP) as www.intechopen.com phosphate donors (Johnson & Fridland, 1989). Didanosine-MP is then converted to ddAMP by adenylosuccinate synthetase and 5' adenosine monophosphate-activated protein (AMP) kinase (Ahluwalia et al, 1987). The enzymes involved in phosphorylation of ddAMP to ddADP and ddATP have not been identified, although AMP kinase and NDP kinase have been proposed to play a role.…”