Targeted isolation and identification of isoquinoline alkaloids from Xylopia ferruginea bark with anti Aβ-induced...

A comprehensive ¹³C NMR-based dereplication and LC-MS/MS based-molecular networking analyses were performed on the bark extract of Xylopia ferruginea (Hook.f. Thomson) and led to the discovery of fifteen isoquinoline alkaloids; lysicamine (1), liriodenine (2), O-methylmoschatoline (3), anonaine (4), norlirioferine (5), isoboldine (6), columbamine (7), jatrorrhizine (8), palmatine (9), nuciferine (10), roemerine (11), N-methylasimilobine (12), N-methylasimilobine N-oxide (13), stephanine (14) and isocorydine (15). Further purification led to the isolation of one new compound, 4,5-dihydro-2-hydroxy-1-methoxy-7H-dibenzo[de,g]quinolin-7-one (16), and four known compounds; lysicamine (1), liriodenine (2), nuciferine (10) and roemerine (11). Selected alkaloid isolates were evaluated for neuroprotective activity in a transgenic Caenorhabditis elegans model expressing human amyloid-beta (Aβ). Lysicamine (1) and liriodenine (2), exhibited moderate neuroprotective activity with paralysis delayed by 1.1 h and 0.5 h, respectively. This study highlights the chemical profile and neuroprotective activity of isoquinoline alkaloids from X. ferruginea and underscores the utility of integrative dereplication and molecular networking approaches in natural product discovery.