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

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.