Inhibition of mitochondrial metabolism by (-)-jerantinine A: synthesis and biological studies in triple-negative breast cancer cells

  • RSC Med Chem. 2023 Mar 1;14(4):710-714. doi: 10.1039/d3md00049d.
Timothy L Gialelis  1 ,  Zifei Wang  2 ,  Joshua A Homer  2 ,  Wen-Hsuan Yang  2 ,  Taemoon Chung  2 ,  Qingting Hu  2  3 ,  Christopher J Smedley  1 ,  Nitin J Pawar  2 ,  Nitinkumar S Upadhyay  2 ,  David A Tuveson  2 ,  Scott K Lyons  2 ,  Michael J Lukey  2 ,  John E Moses  2
Affiliations
  • 1. La Trobe Institute for Molecular Science, La Trobe University Melbourne VIC 3086 Australia.
  • 2. Cancer Center, Cold Spring Harbor Laboratory 1 Bungtown Road Cold Spring Harbor NY 11724 USA [email protected] [email protected].
  • 3. Graduate Program in Genetics, Stony Brook University Stony Brook NY 11794 USA.
PMID: 37122543 DOI: 10.1039/d3md00049d
Abstract

A concise semi-synthesis of the Aspidosperma Alkaloids, (-)-jerantinine A and (-)-melodinine P, and derivatives thereof, is reported. The novel compounds were shown to have potent activity against MDA-MB-231 triple-negative breast Cancer cells. Furthermore, unbiased metabolomics and live cell reporter assays reveal (-)-jerantinine A alters cellular redox metabolism and induces oxidative stress that coincides with cell cycle arrest.