The fungal natural product (1S,3S)-austrocortirubin induces DNA damage in HCT116 cells via a mechanism unique from other DNA damaging agents
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Islam, Md Amirul
Davis, Rohan A
McAlpine, Shelli R
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Abstract
Screening a series of natural product-based tetrahydroanthraquinones led to the identification of a novel molecule, (1S,3S)-austrocortirubin (2), which acts via inducing DNA damage. Compound 2 has a GI50 of 3 μM against HCT116 and induces apoptosis. Mechanism of action studies indicate that it causes significant DNA damage during G0/G1, S, and G2 cell cycle phases. Cells are stopped at the G2/M phase checkpoint, and do not reach mitosis due to large amounts of DNA damage. Thus, compound 2 exhibits a unique mechanism of action, one that is distinct from doxorubicin, despite the high degree of structural homology between these two quinone-based structures.
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Bioorganic and Medicinal Chemistry Letters
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25
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2
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© 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
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Medicinal and biomolecular chemistry
Medicinal and biomolecular chemistry not elsewhere classified
Organic chemistry
Pharmacology and pharmaceutical sciences