Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism

Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse colle...

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Bibliographic Details
Published in:Medicinal chemistry research 2021-03, Vol.30 (3), p.635-646
Main Authors: Schilf, Paul, Srinivasulu, Vunnam, Bolognesi, Maria L., Ibrahim, Saleh, Majdalawieh, Amin F., Abu-Yousef, Imad A., Omar, Hany A., ElAwady, Raafat, Al-Tel, Taleb H.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Cell proliferation
Cycloaddition
Hepatoma
Inorganic Chemistry
Lymphocytes B
Medicinal Chemistry
Membrane potential
Mitochondria
Modulators
Natural products
Original Research
Pharmacology/Toxicology
Reactive oxygen species
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Summary:Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3 + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane potential, elevate reactive oxygen species content, and deplete ATP content in a hepatoma cell line (Hepa1-6), without affecting the proliferation of T- or B-cells. This selective targeting represents a new approach for the treatment of cancer.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-020-02669-3