3-Deazaadenosine hydrochloride is an inhibitor of S-adenosylhomocysteine hydrolase (Ki: 3.9 µM). It has anti-inflammatory, anti-proliferative, and anti-HIV activity.

HIV-1 (A018 isolate):0.20 µM , HIV-1 (A012 isolate):0.15, S-adenosylhomocysteine hydrolase:(ki)3.9 µM

3-Deazaadenosine exhibits antiviral properties specifically against HIV, by inhibiting the p24 antigen in HIV-1 infected peripheral blood mononuclear (PBMCs) cells (A012 and A018 isolates, IC50s: 0.15 and 0.20 μM) [1]. Furthermore, it modulates inflammatory responses by suppressing LPS-induced TNF-α mRNA expression and altering NF-κB pathway activity in RAW 264.7 cells. This includes inhibition of NF-κB transcriptional activity, which is enhanced by homocysteine, and proteolytic degradation of IκBα (not IκBβ), despite increasing NF-κB's DNA binding activity and promoting its nuclear translocation [2]. Additionally, at concentrations of 50 and 100 μM, 3-Deazaadenosine impedes the phosphorylation of several key signaling molecules, including Raf, ERK, protein-dependent kinase 1, protein kinase B (Akt), and forkhead transcription factor FoxO1a. At 50 μM, it also inhibits the proliferation of vascular smooth muscle cells (VSMC) by interfering with Ras signaling pathways, showcasing its potential for cardiovascular applications [3].

The HIV-1 strains A012 and A018 are used in the assay. Inhibition of p24 antigen is measured. Briefly, PHA-stimulated peripheral blood mononuclear (PBMCs) are incubated with either HIV-1 strain for 1 h at 37°C at 200-fold the 50% tissue culture infectious dose (TCID50) of the virus stock per 2 × 10^5 PBMC cells. The TCID50 is defined as the amount of virus stock at which 50% of the inoculated wells are positive. Cells are then grown in microtiter plates with different drug concentrations at 2 × 10^5 cells per well. On day 4, cells are resuspended and split 1:3 with fresh media and 3-Deazaadenosine. Supernatant p24 antigen is determined on day 7 by ELISA [1].