Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase

AUTOR(ES)

Sudbeck, Elise A.

FONTE

American Society for Microbiology

RESUMO

Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, <1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 μM.

Documentos Relacionados

• Protein structure-based design of potent orally bioavailable, nonpeptide inhibitors of human immunodeficiency virus protease.
• Structure-based design of nonpeptide inhibitors specific for the human immunodeficiency virus 1 protease.
• Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors
• Structure-Based Design and Engineering of a Nontoxic Recombinant Pokeweed Antiviral Protein with Potent Anti-Human Immunodeficiency Virus Activity
• Seeking novel leads through structure-based pharmacophore design