Argentatin C Analogues with Potential Antinociceptive Activity and Other Triterpenoid Constituents from the Aerial Parts of Parthenium incanum .

Four new triterpenes, 25-dehydroxy-25-methoxyargentatin C ( 1 ), 20 S -hydroxyargentatin C ( 2 ), 20 S -hydroxyisoargentatin C ( 3 ), and 24- epi -argentatin C ( 4 ), together with 10 known triterpenes ( 5 - 14 ) were isolated from the aerial parts of Parthenium incanum . The structures of 1 - 4 were elucidated by detailed analysis of their spectroscopic data, and the known compounds 5 - 14 were identified by comparison of their spectroscopic data with those reported. Since argentatin C ( 11 ) was found to exhibit antinociceptive activity by decreasing the excitability of rat and macaque dorsal root ganglia (DRG) neurons, 11 and its new analogues 1 - 4 were evaluated for their ability to decrease the excitability of rat DRG neurons. Of the argentatin C analogues tested, 25-dehydroxy-25-methoxyargentatin C ( 1 ) and 24- epi -argentatin C ( 4 ) decreased neuronal excitability in a manner comparable to 11 . Preliminary structure-activity relationships for the action potential-reducing effects of argentatin C ( 11 ) and its analogues 1 - 4 , and their predicted binding sites in pain-relevant voltage-gated sodium and calcium channels (VGSCs and VGCCs) in DRG neurons are presented.