Isolation, Structural Elucidation, and Anti-HIV Activity of Daphnane Diterpenoids from <i>Daphne odora</i>

Otsuki, Kouharu; Li, Wei; Miura, Kasumi; Asada, Yujiro; Huang, Li; Chen, Chin Ho; Lee, Kuo‐Hsiung; Koike, Kazuo

doi:10.1021/acs.jnatprod.0c00540

Cited by 19 publications

(9 citation statements)

References 23 publications

(21 reference statements)

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“…The HIV inhibitory effect and latency reversal activity of daphnane diterpenoids have been reported previously for compounds isolated from other Gnidia species [ 35 ]. However, we show here, for the first time, that these compounds are also present in G. sericocephala roots, a readily-available plant traditionally used for HIV/AIDS management in South Africa.…”

Section: Discussionmentioning

confidence: 86%

HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala (Thymelaeaceae)

Tembeni

Sciorillo

Invernizzi

et al. 2022

Viruses

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Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The “shock and kill” therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by >80% at 0.08 µg/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 µM without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions.

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Section: Discussionmentioning

confidence: 86%

HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala (Thymelaeaceae)

Tembeni

Sciorillo

Invernizzi

et al. 2022

Viruses

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“…The fifth fraction, 100% MeOH was further fractionated by C 18 preparative HPLC (MeCN-H 2 O 70:30) followed by semi-preparative HPLC using biphenyl column and pentafluorophenyl columns to obtain 1 (8.5 mg), 2 (11.8 mg), 3 (2.5 mg), 4 (5.1 mg), 5 (1.3 mg), 6 (3.7 mg), 7 (2.0 mg) and 8 (1.0 mg). The structures of the compounds were determined by dereplication procedures that consisted of comparisons of experimentally derived NMR, MS, and other spectroscopic data to published data on these compounds [ 19 , 20 , 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

Yuanhuacine Is a Potent and Selective Inhibitor of the Basal-Like 2 Subtype of Triple Negative Breast Cancer with Immunogenic Potential

Fermaintt

Peramuna

Cai

et al. 2021

Cancers

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The heterogeneity of triple negative breast cancer (TNBC) has led to efforts to further subtype this disease with the hope of identifying new molecular liabilities and drug targets. Furthermore, the finding that TNBC is the most inherently immunogenic type of breast cancer provides the potential for effective treatment with immune checkpoint inhibitors and immune adjuvants. Thus, we devised a dual screen to identify compounds from natural product extracts with TNBC subtype selectivity that also promote the expression of cytokines associated with antitumor immunity. These efforts led to the identification of yuanhuacine (1) as a potent and highly selective inhibitor of the basal-like 2 (BL2) subtype of TNBC that also promoted an antitumor associated cytokine signature in immune cells. The mechanism of action of yuanhuacine for both phenotypes depends on activation of protein kinase C (PKC), defining a novel target for the treatment of this clinical TNBC subtype. Yuanhuacine showed potent antitumor efficacy in animals bearing BL2 tumors further demonstrating that PKC could function as a potential pharmacological target for the treatment of the BL2 subtype of TNBC.

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“…A number of potent anti-HIV tigliane diterpenoids from Reutealis trisperma [ 80 ] (IC 50 s 2.30–4.03 μM) and Wikstroemia lamatsoensis [ 81 , 82 ] (IC 50 s 0.18–12.80 nM) have been reported. Recently, nine potent anti-HIV daphnane diterpenoid orthoesters ( 26 – 34 , Table 3 ) ( 30 , Figure 3 ) [ 83 ] and novel gnidimacrin-related macrocyclic daphnanes, daphneodorins A and B ( 35 , 36 , Figure 3 , Table 1 and Table 3 ) [ 40 ], isolated from Daphne odora with EC 50 values of 0.16–7.70 nM were reported. Potent anti-HIV daphnane diterpenes were also isolated from petroleum ether extract of Daphne genkwa [ 84 ].…”

Section: Selected Bioactive Natural Products and Analogsmentioning

confidence: 99%

“…SI: selectivity index, the ratio of CC 50 /EC 50 . NR: not reported in the original paper [ 40 , 42 , 76 , 83 ].…”

Section: Selected Bioactive Natural Products and Analogsmentioning

confidence: 99%

Lead/Drug Discovery from Natural Resources

Eichler

Klausner

et al. 2022

Molecules

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Natural products and their derivatives have been shown to be effective drug candidates against various diseases for many years. Over a long period of time, nature has produced an abundant and prosperous source pool for novel therapeutic agents with distinctive structures. Major natural-product-based drugs approved for clinical use include anti-infectives and anticancer agents. This paper will review some natural-product-related potent anticancer, anti-HIV, antibacterial and antimalarial drugs or lead compounds mainly discovered from 2016 to 2022. Structurally typical marine bioactive products are also included. Molecular modeling, machine learning, bioinformatics and other computer-assisted techniques that are very important in narrowing down bioactive core structural scaffolds and helping to design new structures to fight against key disease-associated molecular targets based on available natural products are considered and briefly reviewed.

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Isolation, Structural Elucidation, and Anti-HIV Activity of Daphnane Diterpenoids from Daphne odora

Cited by 19 publications

References 23 publications

HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala (Thymelaeaceae)

HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala (Thymelaeaceae)

Yuanhuacine Is a Potent and Selective Inhibitor of the Basal-Like 2 Subtype of Triple Negative Breast Cancer with Immunogenic Potential

Lead/Drug Discovery from Natural Resources

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