Denbinobin, a naturally occurring 1,4-phenanthrenequinone, inhibits HIV-1 replication through an NF-κB-dependent pathway

Anthraquinones and structurally related compounds have been recently shown to exert antiviral activities and thus exhibit a therapeutic potential. In this study we report the isolation of the 1,4-phenanthrenequinone, denbinobin, from a variety of Cannabis sativa. Denbinobin does not affect the reverse transcription and integration steps of the viral cycle but prevents HIV-1 reactivation in Jurkat T cells activated by TNFα, mAbs anti-CD3/CD28 or PMA. In addition, denbinobin inhibits HIV-1-LTR activity at the level of transcription elongation and also TNFα-induced HIV-1-LTR transcriptional activity. We found that denbinobin prevents the binding of NF-κB to DNA and the phosphorylation and degradation of NF-κB inhibitory protein, IκBα, and inhibits the phosphorylation of the NF-κB p65 subunit in TNFα-stimulated cells. These results highlight the potential of the NF-κB transcription factor as a target for natural anti-HIV-1 compounds such as 1,4-phenanthrenequinones, which could serve as lead compounds for the development of an alternative therapeutic approach against AIDS.