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Article

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

1
Interdisciplinary Excellence Centre, Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary
2
Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
3
Department of Medical Physiology, School of Medicine, University of Nairobi, Nairobi P.O. Box 30197-00100, Kenya
4
Department of Medical Chemistry, University of Szeged, H-6720 Szeged, Hungary
5
Interdisciplinary Centre of Natural Products, University of Szeged, H-6720 Szeged, Hungary
*
Authors to whom correspondence should be addressed.
Academic Editor: Daniela De Vita
Pharmaceuticals 2021, 14(7), 653; https://doi.org/10.3390/ph14070653
Received: 3 June 2021 / Revised: 27 June 2021 / Accepted: 30 June 2021 / Published: 7 July 2021
(This article belongs to the Special Issue Antiviral Compounds in Medicinal Plants)
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 (19, 1417, 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 1214 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. View Full-Text
Keywords: Euphorbia usambarica; diterpenoid; usambariphane; HIV; latency reactivation; latency reversal agent; PKC Euphorbia usambarica; diterpenoid; usambariphane; HIV; latency reactivation; latency reversal agent; PKC
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MDPI and ACS Style

Tsai, Y.-C.; Nell, R.A.; Buckendorf, J.E.; Kúsz, N.; Mwangi, P.W.; Berkecz, R.; Rédei, D.; Vasas, A.; Spivak, A.M.; Hohmann, J. Bioactive Compounds from Euphorbia usambarica Pax. with HIV-1 Latency Reversal Activity. Pharmaceuticals 2021, 14, 653. https://doi.org/10.3390/ph14070653

AMA Style

Tsai Y-C, Nell RA, Buckendorf JE, Kúsz N, Mwangi PW, Berkecz R, Rédei D, Vasas A, Spivak AM, Hohmann J. Bioactive Compounds from Euphorbia usambarica Pax. with HIV-1 Latency Reversal Activity. Pharmaceuticals. 2021; 14(7):653. https://doi.org/10.3390/ph14070653

Chicago/Turabian Style

Tsai, Yu-Chi, Racheal A. Nell, Jonathan E. Buckendorf, Norbert Kúsz, Peter W. Mwangi, Róbert Berkecz, Dóra Rédei, Andrea Vasas, Adam M. Spivak, and Judit Hohmann. 2021. "Bioactive Compounds from Euphorbia usambarica Pax. with HIV-1 Latency Reversal Activity" Pharmaceuticals 14, no. 7: 653. https://doi.org/10.3390/ph14070653

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