LC-MS guided isolation of three pairs of enantiomeric alkaloids from Macleaya cordata and their enantioseparations, antiproliferative activity, apoptosis-inducing property

Abstract

(±)-Macleayins F-H (1-3), three pairs of new enantiomeric alkaloid dimers, along with four known alkaloids (4-7) as their plausible biogenetic precursors, were isolated from the aerial parts of Macleaya cordata. Compounds 1-3 were obtained under the guidance of LC-MS investigation, and their structures were elucidated by analysis of the 1D and 2D NMR spectroscopic data. The racemic mixtures were successfully separated by chiral HPLC, and the absolute configurations of enantiomers were determined by electronic circular dichroism (ECD) spectroscopy. Compounds 1-7 showed antiproliferative activity against HL-60 with IC50 values of 1.34-41.30 μM, especially compounds 1-2 exhibited the best inhibitory activity against HL-60 cell lines. In addition, the preliminary mechanism investigation for compound 2 using Annexin V/7-AAD double-staining assay, DAPI staining assay and JC-1 staining method, indicated that 2 inhibited cancer cell proliferation potentially through inducing apoptosis via the mitochondria-related pathway and arrested cell cycle of HL-60 cells at S phase.