Bioactive alkaloids from the stems of Piper magen, an edible spice in Yunnan, China

A pair of amide enantiomers, (+)-magenamide B [(+)-1] and (-)-magenamide B [(-)-1], and six undescribed alkaloids, magenamides CF (2-5), along with 2-nonyl-3,5-dioctylpyridine (6) and 3-decyl-2-nonyl-5-octylpyridine (7), together with 19 known compounds (8-26) were isolated from the stems of Piper magen (Piperaceae). The chemical structures of all the new compounds were elucidated using NMR and MS data. Magenamide C and 5,6-dihydro-1-[(2E)-3-(4-methoxyphenyl)-1-oxo-2-propen-1-yl]-2(1H)-pyridinone (15) strongly inhibited NO production, with IC₅₀ values of 30.09 μM and 3.16 μM, respectively (positive control: L-NMMA, IC₅₀ = 42.24 μM). Moreover, corydalisin C (24) showed DPPH radical scavenging activity, with an IC₅₀ value of 26.10 μM (positive control: Trolox, IC₅₀ = 21.38 μM). Compound 15 and magenamide A demonstrated protective effects against corticosterone-induced neuronal injury at a concentration of 2 μM (P < 0.001). 1-(m-Methoxycinnamoyl)pyrrolidine (16) exhibited BACE1 inhibitory activity, with an IC₅₀ value of 8.73 μM (positive control: LY2886721, IC₅₀ = 31.80 nM).