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

Euphorbia usambarica is a traditional medicine used for gynecologic, endocrine, and urogenital illnesses in East Africa; however, its constituents bioactivities have not been investigated. A variety of compounds isolated from species shown to activity against latent HIV-1, the major source HIV-1 persistence despite antiretroviral therapy. We performed bioactivity-guided isolation identify 15 new diterpenoids (1–9, 14–17, 19, 20) along with 16 known E. latency reversal activity. Euphordraculoate C (1) exhibits rare 6/6/3-fused ring system 2-methyl-2-cyclopentenone moiety. Usambariphanes (2) B (3) display an unusual lactone constructed between C-17 C-2 jatrophane structure. 4β-Crotignoid K (14) revealed 250-fold improvement compared crotignoid (13), identifying that configuration at C-4 tigliane critical The primary mechanism active 12–14 21 was activation PKC, while lignans 26 27 did increase CD69 expression, suggesting non-PKC mechanism. Accordingly, natural potential contribute development eradication strategies.