ent-Pimarane diterpenoids from Siegesbeckia glabrescens with anti-inflammatory activity

Abstract

Nine new ent-pimarane-type diterpenoids, siegesbeckia A-I (1-9), together with four known analogues ent-3α,15,16,19-tetrahydroxypimar-8(14)-ene (10), 15,16-dihydroxypimar-8(14)-en-3-one (11), 14β,16-epoxy-7-pimarene-3α,15β-diol (12) and darutigenol (13), were obtained from the aerial parts of Siegesbeckia glabrescens Makino. The structures of these compounds were elucidated by the interpretation of HRESIMS, 1D NMR and 2D NMR data. Their configurations were determined by ECD analysis and the structure of compound 1 was confirmed by X-ray crystallography. Putative biosynthetic pathways were proposed for 1-13. The anti-inflammatory effects of the compounds were evaluated by testing their inhibition of LPS-induced NO production in BV2 microglial cells. The results revealed that new compounds 2, 6 and 8 exhibited potent inhibitory activities with IC₅₀ values of 33.07, 42.39 and 63.26 μM, which compared well with the positive control minocycline (IC₅₀ 32.84 μM).

Keywords: Anti-inflammatory; Diterpenoids; Siegesbeckia glabrescens Makino; ent-Pimarane-type.