The fungal natural product (1S, 3S)-austrocortirubin induces DNA damage in HCT116 cells via a mechanism unique from other DNA damaging agents. Issue 2 (15th January 2015)

• Record Type: Journal Article
• Authors: Wang, Yao; Islam, Md. Amirul; Davis, Rohan A.; McAlpine, Shelli R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 2(2015)
• Page Start: 249
• Page End: 253
• Publication Date: 2015-01-15
• Subjects: DMSO dimethyl sulfoxide -- GI50 inhibitory concentration (50%) -- Dox doxorubicin -- PAC paclitaxel -- CIS cisplatin; Doxorubicin -- (1S, 3S)-Austrocortirubin -- Tetrahydroanthraquinone -- Anticancer -- HCT116 -- DNA intercalators -- DNA damage; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2014.11.055
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Screening a series of natural product-based tetrahydroanthraquinones led to the identification of a novel molecule, (1 S, 3 S )-austrocortirubin (2 ), which acts via inducing DNA damage. Compound2 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, compound2 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.