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

Abstract

Euphorbia usambarica 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 Euphorbia 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 (1–9, 14–17, 19, and 20) along with 16 known compounds from E. usambarica with HIV-1 latency reversal activity. Euphordraculoate C (1) exhibits a rare 6/6/3-fused ring system with a 2-methyl-2-cyclopentenone moiety. Usambariphanes A (2) and B (3) display an unusual lactone ring constructed between C-17 and C-2 in the jatrophane structure. 4β-Crotignoid K (14) revealed a 250-fold improvement in latency reversal activity compared to crotignoid K (13), 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 12–14 and 21 for the HIV-1 latency reversal activity was activation of PKC, while lignans 26 and 27 that did not increase CD69 expression, suggesting a non-PKC mechanism. Accordingly, natural constituents from E. usambarica have the potential to contribute to the development of HIV-1 eradication strategies.

Potential Effects of Romanian Propolis Extracts against Pathogen Strains

“…A high percentage of all the available therapeutic drugs are derived from natural plants, microbes or animal compounds [ 7 ]. Terrestrial and aquatic species of plants and microorganisms produce unique bioactive substances that can help in the development of standardized phytomedicines with proof of quality, safety and efficacy [ 4 , 5 , 7 , 8 , 9 , 10 , 11 ].…”

Euphorbiaditerpenoids: isolation, structure, bioactivity, biosynthesis, and synthesis (2013–2021)

“…Aromatic abietanes 7–13 feature a benzene ring C. 45–48 Abietane lactones 14–86 comprise an α,β-unsaturated-γ-lactone ring bridging C-12 and C-13. Among them, 16 from E. lunulate is the first example of a formiate ester-containing abietane diterpenoid found in this genus.…”

“…147,148 Similar diterpenoids include usambaricinophanes C–E ( 560–562 ) from E. usambarica . 48 Euphosorophane E ( 563 ) 147 and isoterracinolide C ( 564 ) 48 are bishomojatrophanes containing an eight-membered lactone, whereas usambaricinophanes A and B ( 565 and 566 ) are bishomojatrophanes bearing a nine-membered lactone. 48 Secoheliosphanes A and B ( 567 and 568 ) and euphelioscopnoid A ( 569 ) from the whole plants of E. helioscopia are novel 7,8-secojatrophanes and 9,10-secojatrophanes, respectively.…”

“…48 Euphosorophane E ( 563 ) 147 and isoterracinolide C ( 564 ) 48 are bishomojatrophanes containing an eight-membered lactone, whereas usambaricinophanes A and B ( 565 and 566 ) are bishomojatrophanes bearing a nine-membered lactone. 48 Secoheliosphanes A and B ( 567 and 568 ) and euphelioscopnoid A ( 569 ) from the whole plants of E. helioscopia are novel 7,8-secojatrophanes and 9,10-secojatrophanes, respectively. 105,149 Secoheliosphanes A and B are proposed to be derived from 2- epi -euphornin I ( 329 ) and euphoscopin A ( K1 ), two co-occurring diterpenoids via enzymatically catalyzed retro-aldol reaction.…”

“…Chemical research on the roots of E. ebracteolata afforded a rare 14(13 → 12)- abeo -tigliane diterpenoid ( 817 ). 66 Euphordraculoate A ( 818 ) 177 and euphordraculoate C ( 819 ) 48 are two 4,5- seco -tigliane lactones, which were isolated from E. dracunculoides and E. usambarica , respectively. Either euphodendriane A ( K7 ) or 4,20-dideoxy-5-hydroxyphorbol-12-13-isobutyrate ( K8 ), two co-occurring diterpenoids, is the biosynthetic precursor of 818 .…”