Design, synthesis, and biological evaluation of novel substituted [1,2,3]triazolo[4,5‑ d ]pyrimidines as HIV-1 Tat-TAR interaction inhibitors

A novel series of compounds, derived from (1,2,3)triazolo(4,5-d)pyrimidines with a guanidyl group or amino group-terminated side chain was designed and synthesized as HIV-1 trans-activator of transcription-trans-activation responsive region (Tat-TAR) inter - action inhibitors. Their ability to inhibit Tat-TAR RNA interaction was determined by a Tat- dependent HIV-1 long terminal repeat (LTR)-driven chloramphenicol acetyltransferase (CAT) assay and simian immunodeficiency virus (SIV)-induced syncytium evaluation. The binding of the compounds with TAR RNA was conducted by molecular modeling and capil- lary electrophoresis (CE) analysis. The results showed that all the compounds could block the Tat-TAR interaction and have antiviral activities.