Synthesis and Optimization of Nitroxide-Based Inhibitors of Ferroptotic Cell Death in Cancer Cells and Macrophages.
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ABSTRACT:
SUBMITTER: Charaschanya M
PROVIDER: S-EPMC8919392 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Synthesis and Optimization of Nitroxide-Based Inhibitors of Ferroptotic Cell Death in Cancer Cells and Macrophages.
Charaschanya Manwika M Maskrey Taber S TS LaPorte Matthew G MG Janjic Jelena M JM Wipf Peter P
ACS medicinal chemistry letters 20220204 3
JP4-039 is an alkene peptide isostere that acts as a low-micromolar inhibitor of erastin- and RSL-3-induced ferroptotic cell death in the HT-1080 cell line. In this work, we have developed new synthetic strategies that allow access to analogues of this lead structure. Enantioselective vinylogous Mannich or cross-metathesis reactions were key to the preparation of a series of analogues that culminated in the preparation of the <i>ca.</i> 30-fold more potent analogue (<i>S</i>)-<b>6c</b>. Structur ...[more]
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