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Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl-tethered anthraquinones

Errington, Rachel J., Sadiq, Maria, Cosentino, Laura, Wiltshire, Marie, Sadiq, Omair, Sini, Marcella, Lizano, Enric, Pujol, Maria D., Morais, Goreti R. and Pors, Klaus 2018. Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl-tethered anthraquinones. Bioorganic and Medicinal Chemistry Letters 28 (8) , pp. 1274-1277. 10.1016/j.bmcl.2018.03.040

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Abstract

Structural features from the anticancer prodrug nemorubicin (MMDX) and the DNA-binding molecule DRAQ5™ were used to prepare anthraquinone-based compounds, which were assessed for their potential to interrogate cytochrome P450 (CYP) functional activity and localisation. 1,4-disubstituted anthraquinone 8 was shown to be 5-fold more potent in EJ138 bladder cancer cells after CYP1A2 bioactivation. In contrast, 1,5-bis((2-morpholinoethyl)amino) substituted anthraquinone 10 was not CYP-bioactivated but was shown to be fluorescent and subsequently photo-activated by a light pulse (at a bandwidth 532–587 nm), resulting in punctuated foci accumulation in the cytoplasm. It also showed low toxicity in human osteosarcoma cells. These combined properties provide an interesting prospective approach for opto-tagging single or a sub-population of cells and seeking their location without the need for continuous monitoring.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0960-894X
Date of First Compliant Deposit: 11 May 2018
Date of Acceptance: 15 March 2018
Last Modified: 28 Apr 2019 12:42
URI: http://orca.cf.ac.uk/id/eprint/111385

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