Phyllanthusols A and B, Cytotoxic Norbisabolane Glycosides from Phyllanthus acidus Skeels

Vongvanich, Namphung; Kittakoop, Prasat; Kramyu, Jarin; Tanticharoen, Morakot; Thebtaranonth, Yodhathai

doi:10.1021/jo000439+

Cited by 43 publications

(14 citation statements)

References 10 publications

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“…Phllanthacidoid A (PA) is a structurally unique and complex anti-HBV norbisabolane sesquiterpene (Figure S1a and Table S1) that was originally isolated and identified from a Phyllanthus spp. used to treat HBV infection by local people of Yunnan province, China 3, 13,14 . Our prior structure-activity relationship (SAR) study of PA derivatives 13 , suggested that the ester substitution (C-15) is critical to the antiviral activity.…”

Section: Results Pac5 Inhibits Hbv Infectionmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein A2B1, a novel drug target for hepatitis B virus infection

Chen

Yuan

et al. 2021

Preprint

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HBV infection is a major global health burden that needs novel immunotherapeutic approaches. Herein, we show that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a novel drug target for HBV infection. We reveal the new target with highly selective probes of PAC5, a natural sesquiterpene derivative. PAC5 show potent anti-HBV activity in vivo and in vitro. Further studies on its mode of action indicate that PAC5 binds to the residue Asp49 and a deep groove in the RNA recognition motif1 (RRM1) region of hnRNPA2B1. PAC5-bound hnRNPA2B1 is activated, dimerized, and translocated to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to the production of type I interferons (IFNs). Furthermore, PAC5 also suppresses other viral replications, such as SARS-CoV-2 and vesicular stomatitis virus (VSV). Our results indicate that PAC5 is the first small molecule agonist of hnRNPA2B1, a drug target potentially valid for broad-spectrum viral infections, providing a novel strategy for viral immunotherapy.

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Section: Results Pac5 Inhibits Hbv Infectionmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein A2B1, a novel drug target for hepatitis B virus infection

Chen

Yuan

et al. 2021

Preprint

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“…76 The roots of Phyllanthus emblica 77,78 contain phyllaemblic acid 64, its methyl ester 65 and several glycosides, whilst phyllanthusol A and phyllanthusol B, which possess the aglycones 66 and 67, respectively, have been found in another species of this genus, Phyllanthus acidus. 79 A new antibacterial bisabolane sesquiterpene 68 has been isolated from Ligularia thyrsoidea. 80 Proposals for the biogenesis and absolute configuration of twelve heliannane sesquiterpenes, based on a modified Mosher method, have been presented.…”

Section: Bisabolanementioning

confidence: 99%

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2001

Nat. Prod. Rep.

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“…Highly oxygenated bisabolane sesquiterpenoids are mainly found in plants of the Phyllanthus genus − and less frequently in the Glochidion genus, , and most of them exist as glycosides. The first example, phyllanthocin, with strong antileukemic activity, was obtained from P. brasiliensis Muell .…”

Section: Introductionmentioning

confidence: 99%

Anti-Hepatitis B Virus Norbisabolane Sesquiterpenoids from Phyllanthus acidus and the Establishment of Their Absolute Configurations Using Theoretical Calculations

Wang

et al. 2014

J. Org. Chem.

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Nineteen new highly oxygenated norbisabolane sesquiterpenoids, phyllanthacidoid acid methyl ester (1), and C-T (4-21), were isolated from Phyllanthus acidus Skeels, together with two known ones, phyllanthusols A (2) and B (3), whose sugar moiety was revised as glucosamine-N-acetate, rather than the previously assigned mannosamine-N-acetate. Compounds 2 and 3 were renamed respectively as phyllanthacidoids A (2) and B (3) to avoid confusion. All of the isolates except for 1 are glycosides, whose saccharide moieties possess a pentaoxy cyclohexane (scyllo quercitol) connecting with glucosamine-N-acetate or glucosyl moieties, which are first examples in natural products. Phyllanthacidoids N-R (15-19) with 8R configurations and/or 5,8-diketal skeleton, are unprecedented structures among norbisabolane sesquiterpenoids. Phyllanthacidoids S (20) and T (21) have the unusual tricyclo [3.1.1.1] oxygen bridge skeleton formed by a diketal system, of which the relative configurations of the aliphatic chain were assigned on the basis of heteronuclear coupling constants. The absolute configurations of compounds (1-21) were established by means of calculated electronic circular dichroism (ECD) and coupling constants. Compounds 1-5, 7-9, 10, and 14 displayed potential anti-hepatitis B virus (HBV) activities, with IC50 values of 0.8-36 μM against HBV surface antigen (HBsAg) and HBV excreted antigen (HBeAg), and the results indicated that the 5-ketal group and sugar moieties had contributions to the selectivity of HBsAg and HBeAg.

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Phyllanthusols A and B, Cytotoxic Norbisabolane Glycosides from Phyllanthus acidus Skeels

Cited by 43 publications

References 10 publications

Heterogeneous nuclear ribonucleoprotein A2B1, a novel drug target for hepatitis B virus infection

Heterogeneous nuclear ribonucleoprotein A2B1, a novel drug target for hepatitis B virus infection

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Anti-Hepatitis B Virus Norbisabolane Sesquiterpenoids from Phyllanthus acidus and the Establishment of Their Absolute Configurations Using Theoretical Calculations

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