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.
Highlights
Benzophenanthridine and protopine alkaloids occur in Macleaya cordata (Willd) R
The above data suggested that 1 was a dimeric alkaloid consisting of a chelerythrine and a protopine moiety[5]
In order to further research the apoptosis induced effect of compound 2, the fluorescent probe JC-1 was carried out to detect the changes of mitochondrial membrane potential
Summary
Its1H and 13C NMR data (Table 1) revealed structural similarity to 1, expected that one methylenedioxy in 1 was replaced by two methoxyl groups (δH 3.95, 3.50; δC 56.0, 60.9) It was confirmed by the HMBC correlations of 8-OCH3 with C-8, 7-OCH3/H-6 with C-7; 9′-OCH3/H-8′/H-11′ with C-9′, and of 10′-OCH3/H-11′ with C-10′ (Supplementary Figure S2). Compound 3 showed more similar NMR data (Supplementary Tables S1 and S2) to macleayin B than 1, deducing that the relative configuration of 3 was the same as macleayin B. In order to further research the apoptosis induced effect of compound 2, the fluorescent probe JC-1 was carried out to detect the changes of mitochondrial membrane potential. The results demonstrated that 2 could induce apoptosis in HL-60 cells through mitochondrial-related pathway
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
