(±)-Hypernumqulins A-H: Eight pairs of unexpected [2+2] cycloaddition sesquiterpenoid alkaloid with 6/6/6/4/10 ring system from Hypericum monogynum L.

Bioorg Chem

Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City & Southwest University, SWU-TAAHC Medicinal Plant Joint R&D Centre, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China; Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China. Electronic address:

Published: September 2024

(±)-Hypernumqulins A-H (1-8), eight pairs of enantiomeric quinoline alkaloids fused with an isopentenyl and a germacrane-type sesquiterpenoid, featuring an unprecedented skeleton with 6/6/6/4/10 ring system, were isolated from Hypericum monogynum L. under the guidance of molecular networking strategy. Their structures including absolute configuration were elucidated by NMR spectroscopy analysis, X-ray crystallography and quantum chemical calculation. The proposed [2+2] cycloaddition may play a key biogenic step in building the unexpected skeleton. Most of the isolates exhibited cytotoxicity with IC values ranging from 2.82 ± 0.03 to 45.25 ± 1.26 μM against MCF-7, A549 or SGC7901 cells. Furthermore, compounds (±)-1 and (-)-1 could induce apoptosis by upregulating the protein expression level of Bax and downregulating of Bcl-2 in MCF-7 cells. These findings provided the first example of germacrane sesquiterpene quinoline alkaloids, and supported the possibilities for the development of new anti-tumor agents.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2024.107564DOI Listing

Publication Analysis

Top Keywords

±-hypernumqulins a-h
8
[2+2] cycloaddition
8
6/6/6/4/10 ring
8
ring system
8
hypericum monogynum
8
quinoline alkaloids
8
a-h pairs
4
pairs unexpected
4
unexpected [2+2]
4
cycloaddition sesquiterpenoid
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!