Anti-inflammatory steroidal sapogenins and a conjugated chalcone-stilbene from Dracaena usambarensis Engl.

Four new steroidal sapogenins, dracaenogenins C F (1 – 4), a new conjugated chalcone-stilbene, 3′′-methoxycochinchinenene H (5) together with eight known compounds namely, (25 S)-spirosta-1,4-dien-3-one (6), trans -resveratrol (7), 4,4′-dihydroxy-3′-methoxychalcone (8), N - trans -coumaroyltyramine (9), N - trans - p -coumaroyloctopamine (10), N - trans -feruloyloctopamine (11), 7-hydroxy-1-(4-hydroxy-3-methoxyphenyl)- N 2 , N 3 - bis (4-hydroxyphenethyl)-6-methoxy-1,2-dihydronaphthalene-2,3-dicarboxamide (12) and grossamide (13) were isolated from the stems of Dracaena usambarensis Engl. from Kenya. It is important to note that compounds 12 and 13 are being reported from this genus for the first time. Structural elucidation of the isolated compounds was done using spectroscopic (NMR, UV, IR, optical rotation) and spectrometric (HRESIMS) techniques. The absolute and relative configurations of the isolated compounds were determined by employing single crystal X-ray crystallography analysis, NOESY correlations and coupling constants. The anti-inflammatory potencies of the isolated compounds were evaluated by measuring the levels of four cytokines (IL-1β, IL-2, GM-CSF and TNF-α) in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS). At the tested concentration of 100 μM, the new conjugated chalcone-stilbene 5 , the dihydrochalcone, 8 and the lignanamide, 13 were substantially more potent than the standard drug, ibuprofen, inhibiting the release of all the cytokines, IL-1β , IL-2, GM-CSF and TNF-α from 0.06–58.04% compared to LPS control. These compounds should therefore be considered for development into anti-inflammatory drug candidates. Compound 7 significantly decreased the release of GM-CSF (6.11% of LPS control) and TNF-α (18.35% of LPS control). The cytokine TNF-α was sensitive to all the tested compounds 1 - 13. Unlabelled Image • Thirteen secondary metabolites isolated from the stem bark of Dracaena usambarensis. • Four new steroidal sapogenins, 1 - 4 and a new conjugated chalcone-stilbene, 5. • The relative configuration of 1 was confirmed with X-ray analysis. • Inhibitory activity of 5 , 8 and 13 , was higher than ibuprofen against all cytokines. [ABSTRACT FROM AUTHOR]