Small organic molecules targeting PCAF bromodomain as potent inhibitors of HIV-1 replication

Human p300/CBP associated factor bromodomain (PCAF BRD), a relatively conserved host cell protein, can selectively bind with Tat-AcK50 (tat acetylated lys50). This interaction is essential for the transcription activation of HIV-1 viral gene, therefore PCAF BRD provides a potential targeting protein to inhibit the transcription. We synthesized a series of N1-aryl-propane-1,3-diamine compounds to bind to PCAF BRD. And cellular level anti-HIV-1 assay showed that these small molecules had good inhibitory potency on HIV-1 replication, which was consistent with the molecular assay. Also, it was found that 3-(2-nitrophenoxy) propan-1-amine derivatives had strong bioactivity against HIV-1 replication.