Inhibition of mitochondrial metabolism by (−)-jerantinine A: synthesis and biological studies in triple-negative breast cancer cells. Issue 4 (13th March 2023)

• Record Type: Journal Article
• Authors: Gialelis, Timothy L.; Wang, Zifei; Homer, Joshua A.; Yang, Wen-Hsuan; Chung, Taemoon; Hu, Qingting; Smedley, Christopher J.; Pawar, Nitin J.; Upadhyay, Nitinkumar S.; Tuveson, David A.; Lyons, Scott K.; Lukey, Michael J.; Moses, John E.
• Is Part Of: RSC medicinal chemistry. Volume 14:Issue 4(2023)
• Page Start: 710
• Page End: 714
• Publication Date: 2023-03-13
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1039/d3md00049d
• Languages: English
• ISSNs: 2632-8682

Abstract

Abstract : We report an improved 4-step semisynthesis of (−)-jerantinine A and (−)-melodinine P from (−)-tabersonine, qualify their potency against TNBC cells and confirm they induce oxidative stress. JA also acts as a potent inhibitor of nucleotide metabolism. 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.