Bioactive Compounds from Pax. with HIV-1 Latency Reversal Activity

is a traditional medicine used for gynecologic, endocrine, and urogenital illnesses in East Africa; however, its constituents and bioactivities have not been investigated. A variety of compounds isolated from species have been shown to have activity against latent HIV-1, the major source of HIV-1 persistence despite antiretroviral therapy. We performed bioactivity-guided isolation to identify 15 new diterpenoids (-, -, , and ) along with 16 known compounds from with HIV-1 latency reversal activity. Euphordraculoate C () exhibits a rare 6/6/3-fused ring system with a 2-methyl-2-cyclopentenone moiety. Usambariphanes A () and B () display an unusual lactone ring constructed between C-17 and C-2 in the jatrophane structure. 4-Crotignoid K () revealed a 250-fold improvement in latency reversal activity compared to crotignoid K (), identifying that configuration at the C-4 of tigliane diterpenoids is critical to HIV-1 latency reversal activity. The primary mechanism of the active diterpenoids - and for the HIV-1 latency reversal activity was activation of PKC, while lignans and that did not increase CD69 expression, suggesting a non-PKC mechanism. Accordingly, natural constituents from have the potential to contribute to the development of HIV-1 eradication strategies.