{"doi":"10.3390/ph14070653","title":"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.","journal":"Pharmaceuticals","year":2021,"id":206221,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9421,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":398136,"name":"Racheal A. Nell","orcid":"0000-0002-0324-7522","position":1,"is_corresponding":false},{"id":790583,"name":"Jonathan E. Buckendorf","orcid":null,"position":2,"is_corresponding":false},{"id":790171,"name":"Norbert Kúsz","orcid":"0000-0002-9973-6442","position":3,"is_corresponding":false},{"id":790172,"name":"Peter Waweru Mwangi","orcid":"0000-0002-5013-247X","position":4,"is_corresponding":false},{"id":790173,"name":"Róbert Berkecz","orcid":"0000-0002-9076-2177","position":5,"is_corresponding":false},{"id":790174,"name":"Andrea Vasas","orcid":"0000-0002-1818-7702","position":7,"is_corresponding":false},{"id":263027,"name":"Adam M. Spivak","orcid":"0000-0003-1815-7893","position":8,"is_corresponding":false},{"id":790175,"name":"Judit Hohmann","orcid":"0000-0002-2887-6392","position":9,"is_corresponding":false},{"id":790170,"name":"Yu‐Chi Tsai","orcid":"0000-0002-3131-207X","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:51:37.630221Z","pmid":"34358079","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}