Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues

Novel acyclic nucleoside analogues as inhibitors of HIV-1 RT

Background Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs introduced for treatment of human immunodeficiency virus-1 (HIV-1) infection. These NRTIs may be cyclic or acyclic analogs of natural nucleosides. Both these analogs interact at active site on HIV-RT and compete with indigenous nucleosides/ nucleotides, and thus, divert enzyme activity in manmade direction. All ...

Lethal mutagenesis of HIV with mutagenic nucleoside analogs.

The human immunodeficiency virus (HIV) replicates its genome and mutates at exceptionally high rates. As a result, the virus is able to evade immunological and chemical antiviral agents. We tested the hypothesis that a further increase in the mutation rate by promutagenic nucleoside analogs would abolish viral replication. We evaluated deoxynucleoside analogs for lack of toxicity to human cells...

Anti-HIV activity of new substituted 1,3,4-oxadiazole derivatives and their acyclic nucleoside analogues.

A number of new 5-[(naphthalen-5-yloxy)methyl]-1,3,4-oxadiazole derivatives, 2-5 and 8-11, were synthesized. The 2-{5-[(naphthalen-5-yloxy)methyl]-1,3,4-oxadiazol-2-ylthio}acetohydrazones 6a and 6b were synthesized by the reaction of the hydrazide 4 with the corresponding monosaccharides. Cyclization of the sugar hydrazones 6a and 6b with acetic anhydride afforded the substituted oxadiazoline d...

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first "mechanism validation" phase II clinical trial of a mutagenic base...

Chemical Synthesis of Nucleoside Analogues Chemical Synthesis of Nucleoside Analogues