Cytotoxic alkaloids from the fruit pods of Macleaya microcarpa

Abstract

19 compounds, including seven previously undescribed alkaloids ((-)-macleayin K (1), (+)-macleayin K (2), macleayin M (3), macleayin N (4), macleayin L (5), macleayin O (6), oxohydrastinine A (7), one new natural product (8), and 11 known compounds, were isolated from the fruit pods of Macleaya microcarpa. Their structures were defined based on NMR, HRESIMS, and electronic circular dichroism (ECD) data. A network pharmacology approach combined with molecular docking and in vitro validation was performed to determine the bioactivity, key targets of the 19 compounds against breast cancer (BC) and cervical cancer (CC). EGFR and PIK3CA could become potential therapeutic targets based a network pharmacology. Moreover, molecular docking suggested that the 19 compounds combined well with EGFR and PIK3CA, respectively. Their cytotoxicity of selected compounds was tested against the MCF-7 and HeLa cells, and the preliminary structure-activity relationship is discussed. Compounds 1 (IC₅₀: 6.00 μM) and 2 (IC₅₀: 6.82 μM) exhibited strong inhibitory activity against the HeLa cells and are worthy of further study.

Keywords: Aalkaloids; Cytotoxic activity; Isolation and identification; Macleaya microcarpa; Molecular docking; Network pharmacology; Structure-activity relationship.