TY - JOUR
T1 - Quassinoids
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
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
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.
KW - Picrajavanicins
KW - Picrasma javanica
KW - Quassinoids
KW - Structure–activity relationships
KW - Viral protein R inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84985903430&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2016.08.055
DO - 10.1016/j.bmcl.2016.08.055
M3 - 学術論文
C2 - 27575477
AN - SCOPUS:84985903430
SN - 0960-894X
VL - 26
SP - 4620
EP - 4624
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 19
ER -