3 years ago

Crystal Structures and Human Leukemia Cell Apoptosis Inducible Activities of Parthenolide Analogues Isolated from Piptocoma rufescens

Crystal Structures and Human Leukemia Cell Apoptosis
Inducible Activities of Parthenolide Analogues Isolated from Piptocoma rufescens
Xinxin Li, Jianhua Yu, Lichao Chen, Judith C. Gallucci, A. Douglas Kinghorn, Yulin Ren
The molecular structures of three parthenolide analogues, (−)-goyazensolide (1), (−)-15-deoxygoyazensolide (2), and (−)-ereglomerulide (3), isolated from the leaves of Piptocoma rufescens in a previous study were determined by X-ray analysis, and the absolute configuration of (−)-goyazensolide (1) was confirmed crystallographically using Cu Kα radiation at low temperature. Compounds 13, (+)-rufesolide A (4), and commercial parthenolide were found to be growth inhibitory toward MOLM-13 and EOL-1 human acute myeloid leukemia cells using PKC412 (midostaurin) as the positive control, with 13 being more active than parthenolide. Also, compounds 14 exhibited synergistic effects when tested with PKC412, but parthenolide did not show this type of activity. At a concentration lower than 2.0 μM, both 1 and 2 induced approximately 50% of the cells to become apoptotic at a late stage of the cell cycle, but no similar apoptotic effects were observed for 3, 4, or parthenolide. Leukemia cell apoptosis was induced by these compounds through the activation of caspase-3 and the inhibition of NF-κB, as indicated by immunoblotting analysis, and compounds 1 and 2 seem to be promising leads for development as potential antileukemic agents.

Publisher URL: http://dx.doi.org/10.1021/acs.jnatprod.7b01079

DOI: 10.1021/acs.jnatprod.7b01079

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.