(3,3″)-Linked Biflavanones from Ouratea spectabilis and Their Effects on the Release of Proinflammatory Cytokines in THP-1 Cells

Abstract

Ouratea spectabilis is an arborous species traditionally used in Brazil as an anti-inflammatory agent. Four new (3,3″)-linked biflavanone O-methyl ethers, named ouratein A (1), B (2), C (3), and D (4), were isolated from the bark extract of the species. Ouratein A ( 1) is an enantiomer of neochamagesmine A, which has never been described before. The structures were elucidated by extensive spectroscopic data analyses, whereas their absolute configurations were defined by electronic circular dichroism data. Ouratein D (4) inhibited in vitro the release of the pro-inflammatory cytokine CCL2 by lipopolysaccharide-stimulated THP-1 cells (IC 50 of 3.1 ± 1.1 μM), whereas TNF and IL-1β release were not reduced by any of the biflavanones. These findings show ouratein D (4) as a selective CCL2 inhibitor, which may have potential for the development of new anti-inflammatory agents to prevent or treat cardiovascular diseases.

Biflavanones, Chalconoids, and Flavonoid Analogues from the Stem Bark of Ochna holstii

“…The splitting patterns of the resonances assigned to H-2 (d, J = 10.2 Hz), H-2″ (d, J = 10.0 Hz), H-3 (dd, J = 10.2, 7.8 Hz) and H-3″ (dd, J = 10.0, 7.8 Hz) suggested rings C 1 (H-2/H-3) and C 2 (H-2″/H-3″) to have trans -relative configurations. This conclusion is corroborated by the observed 3 J 2,3 being larger than that (2.3 Hz) reported by Rocha et al for the 2,3- cis -configured analogues, but similar to the 9.2 and 9.9 Hz reported for the trans relative configured analogues . Protons H-3 and H-3″ showed 3 J 3,3″ = 7.8 Hz, which is comparable to the 3 J 3,3″ = 8.5 Hz previously reported for the gauche conformation, but dissimilar to the 3 J 3,3″ = 12.0 Hz of the anti -oriented protons of structurally closely related compounds .…”

“…In addition, the HMBC cross-peaks of proton resonances at δ H 4.50 (H-3) to C-2″ (δ C 86.4), C-4 (δ C 196.0), C-4″ (δ C 200.5), and C-10 (δ C 122.1) and those at δ H 5.62 (H-2) to C-3″ (δ C 60.2), C-4 (δ C 196.0), C-9 (δ C 166.4), and C-2′/6′ (δ C 129.5) established the C-3–C-3″ linkage of the two flavanone units. Similar C-3–C-3″ linkages were previously reported from other plant species including campylospermone B from Campylospermum mannii , ouratein D from Ouratea spectabilis , 4,4,7-tri- O -methylisocapylospermone A from Ochna serrulata , chamaejasmin from Ormocarpum kirkii , and chamaejasmin D from Stellera chamaejasme . The NMR spectroscopic data for compound 1 closely resembled those of campylospermone B and liquiritigeninyl-(1-3,II-3)-naringenin, but had a methoxy group resonating at δ H 3.77 (H-11) and attached to C-7″ (δ C 167.9), indicated by the HMBC cross-peak of H-11 (δ H 3.77) with C-7″ (δ C 167.9).…”

“…The IR spectrum revealed the presence of hydroxy (3396 cm –1 ) and aromatic CC (1604, 1516, and 1453 cm –1 ) groups. UV absorption maxima at 262 and 330 nm indicated the presence of a flavanone-type structure. , …”

“…The structures of the isolated compounds were elucidated by 1D and 2D NMR spectroscopic and mass spectrometric analyses. The known compounds were identified as ouratein D ( 6 ), isochamaejasmin A ( 7 ), , 7′,7″-di- O -methylisochamaejasmin ( 8 ), campylospermone A ( 9 ), liquiritigeninyl-(1-3,II-3)-naringenin ( 10 ), isoliquitigenin ( 11 ), terminalionone ( 12 ), flavumchalcone ( 13 ), lophirone F ( 14 ), 2,3-dihydrocalodenin B ( 15 ), and calodenin B ( 16 ), , by comparison of their spectroscopic data with reported data.…”

“…300 nm, and a negative Cotton effect at ca. 210 nm for the 1 La electronic transition, which indicated a (2 R ) absolute configuration for each flavanone moiety . The absolute configuration at C-3 was determined based on the trans relative configurations of the neighboring H-2 and H-3 protons.…”