The fungal natural product (1S,3S)-austrocortirubin induces DNA damage in HCT116 cells via a mechanism unique from other DNA damaging agents

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Wang, Yao¹  Islam, Md. Amirul¹  Davis, Rohan A.²  McAlpine, Shelli R.¹ 

[1] Univ New S Wales, Dept Chem, Kensington, NSW 2052, Australia

[2] Griffith Univ, Eskitis Inst, Brisbane, Qld 4006, Australia

关键词: Doxorubicin (1S,3S)-Austrocortirubin;    Tetrahydroanthraquinone;    Anticancer;    HCT116;    DNA intercalators;    DNA damage;   

DOI  :  10.1016/j.bmcl.2014.11.055

来源: Elsevier

【 摘 要 】

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 GI(50) of 3 mu M 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. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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