Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl-tethered anthraquinones. Issue 8 (1st May 2018)

• Record Type: Journal Article
• Authors: Errington, Rachel J.; Sadiq, Maria; Cosentino, Laura; Wiltshire, Marie; Sadiq, Omair; Sini, Marcella; Lizano, Enric; Pujol, Maria D.; Morais, Goreti R.; Pors, Klaus
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 8(2018)
• Page Start: 1274
• Page End: 1277
• Publication Date: 2018-05-01
• Subjects: Anthraquinone -- Nemorubicin -- MMDX -- DRAQ5 -- Cytochrome P450 -- CYP1A2 -- Fluorophore -- Cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.03.040
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 anthraquinone8 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 anthraquinone10 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.