Quassinoids: Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection

Nwet Nwet Win; Takuya Ito; Yi Yi Win; Hla Ngwe; Takeshi Kodama; Ikuro Abe; Hiroyuki Morita

doi:10.1016/j.bmcl.2016.08.055

Quassinoids: Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection

Nwet Nwet Win^*, Takuya Ito, Yi Yi Win, Hla Ngwe, Takeshi Kodama, Ikuro Abe, Hiroyuki Morita

^*Corresponding author for this work

Section of Natural Products & Drug Discovery, Division of Medicinal Resources, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl₃-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity. Furthermore, studies of quassinoids (1–15) previously isolated from the extract demonstrated that all of the tested quassinoids exhibit anti-Vpr activity. Among the tested compounds, javanicin I (15) exhibited the most potent anti-Vpr activity (p <0.001) in comparing with that of the positive control, damnacanthal. The structure–activity relationships of the active quassinoids suggested that the presence of a methyl group at C-13 in the 2,12,14-triene-1,11,16-trione-2,12-dimethoxy-18-norpicrasane quassinoids is the important factor for the potent inhibitory effect in TREx-HeLa-Vpr cells.

Original language	English
Pages (from-to)	4620-4624
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2016.08.055
State	Published - 2016

Keywords

Picrajavanicins
Picrasma javanica
Quassinoids
Structure–activity relationships
Viral protein R inhibitors

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2016.08.055

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@article{1d12b3e83ca947139765a6b3a270eb1f,

title = "Quassinoids: Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection",

abstract = "Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl3-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity. Furthermore, studies of quassinoids (1–15) previously isolated from the extract demonstrated that all of the tested quassinoids exhibit anti-Vpr activity. Among the tested compounds, javanicin I (15) exhibited the most potent anti-Vpr activity (p <0.001) in comparing with that of the positive control, damnacanthal. The structure–activity relationships of the active quassinoids suggested that the presence of a methyl group at C-13 in the 2,12,14-triene-1,11,16-trione-2,12-dimethoxy-18-norpicrasane quassinoids is the important factor for the potent inhibitory effect in TREx-HeLa-Vpr cells.",

keywords = "Picrajavanicins, Picrasma javanica, Quassinoids, Structure–activity relationships, Viral protein R inhibitors",

author = "Win, {Nwet Nwet} and Takuya Ito and Win, {Yi Yi} and Hla Ngwe and Takeshi Kodama and Ikuro Abe and Hiroyuki Morita",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd",

year = "2016",

doi = "10.1016/j.bmcl.2016.08.055",

language = "英語",

volume = "26",

pages = "4620--4624",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T2 - Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection

AU - Win, Nwet Nwet

AU - Ito, Takuya

AU - Win, Yi Yi

AU - Ngwe, Hla

AU - Kodama, Takeshi

AU - Abe, Ikuro

AU - Morita, Hiroyuki

PY - 2016

Y1 - 2016

N2 - Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl3-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity. Furthermore, studies of quassinoids (1–15) previously isolated from the extract demonstrated that all of the tested quassinoids exhibit anti-Vpr activity. Among the tested compounds, javanicin I (15) exhibited the most potent anti-Vpr activity (p <0.001) in comparing with that of the positive control, damnacanthal. The structure–activity relationships of the active quassinoids suggested that the presence of a methyl group at C-13 in the 2,12,14-triene-1,11,16-trione-2,12-dimethoxy-18-norpicrasane quassinoids is the important factor for the potent inhibitory effect in TREx-HeLa-Vpr cells.

AB - Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl3-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity. Furthermore, studies of quassinoids (1–15) previously isolated from the extract demonstrated that all of the tested quassinoids exhibit anti-Vpr activity. Among the tested compounds, javanicin I (15) exhibited the most potent anti-Vpr activity (p <0.001) in comparing with that of the positive control, damnacanthal. The structure–activity relationships of the active quassinoids suggested that the presence of a methyl group at C-13 in the 2,12,14-triene-1,11,16-trione-2,12-dimethoxy-18-norpicrasane quassinoids is the important factor for the potent inhibitory effect in TREx-HeLa-Vpr cells.

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Quassinoids: Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection

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Keywords

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