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.
authors: Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan; Department of Chemistry, University of Yangon, Yangon 11041, Myanmar. Electronic address: nwetwin2012@gmail.com.
authors: Nwet Nwet
authors: NN
authors: Win
authors: Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan.
authors: Takuya
authors: T
authors: Ito
authors: Department of Chemistry, University of Yangon, Yangon 11041, Myanmar.
authors: Yi Yi
authors: YY
authors: Win
authors: Department of Chemistry, University of Yangon, Yangon 11041, Myanmar.
authors: Hla
authors: H
authors: Ngwe
authors: Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan.
authors: Takeshi
authors: T
authors: Kodama
authors: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Ikuro
authors: I
authors: Abe
authors: Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan. Electronic address: hmorita@inm.u-toyama.ac.jp.
authors: Hiroyuki
authors: H
authors: Morita
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016336:Gene Products, vpr / Q000037:antagonists & inhibitors*; D015658:HIV Infections / Q000188:drug therapy*; D006367:HeLa Cells; D006801:Humans; D002052:Myanmar; D032270:Picrasma / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry*; D036702:Quassins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D016336:Gene Products, vpr; D036702:Quassins
keywords: Picrajavanicins; Picrasma javanica; Quassinoids; Structure–activity relationships; Viral protein R inhibitors