Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia

• Published in: Bioorganic & medicinal chemistry letters 2010-03, Vol.20 (6), p.1837-1839
• Main Authors: Tamura, Satoru, Kaneko, Masafumi, Shiomi, Atsushi, Yang, Guang-Ming, Yamaura, Toshiaki, Murakami, Nobutoshi
• Format: Article
• Language: English
• Subjects: (10 E,12 Z)-9-hydroxyoctadeca-10,12-dienoic acid; Anti-HIV; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Chromatography, High Pressure Liquid; Gene Products, rev - metabolism; General pharmacology; Malvaceae - metabolism; Medical sciences; NES non-antagonistic inhibitor; Nuclear Export Signals; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - pharmacology; Protein Transport - drug effects; Rev-export inhibitor; Sida cordifolia
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.01.165

As an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev, (10 E,12 Z)-9-hydroxyoctadeca-10,12-dienoic acid ( 1) was disclosed. Additionally, structure–activity relationship analysis clarified cooperation of several functionalities in potency of 1. Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10 E,12 Z)-9-hydroxyoctadeca-10,12-dienoic acid ( 1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure–activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1.