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

Timothy L. Gialelis, Zifei Wang,Joshua A. Homer,Wen-Hsuan Yang,Taemoon Chung, Qingting Hu,Christopher J. Smedley, Nitin J. Pawar,Nitinkumar S. Upadhyay,David A. Tuveson,Scott K. Lyons,Michael J. Lukey,John E. Moses

RSC MEDICINAL CHEMISTRY（2023）

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摘要

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.

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关键词

mitochondrial metabolism,cancer cells,breast cancer,triple-negative

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