PMID: 9000584Jan 1, 1997Paper

Flow cytometric analysis and confocal imaging of anticancer alkylaminoanthraquinones and their N-oxides in intact human cells using 647-nm krypton laser excitation

Cytometry
P J SmithJ V Watson

Abstract

Flow cytometry and laser-scanning confocal fluorescence microscopy have been used in the study of the pharmacodynamics, in single intact cells, of two novel alkylaminoanthraquinones (AQ4 and AQ6), structurally based upon the mid-red excitable but very weakly fluorescent anticancer agent mitoxantrone, together with their respective N-oxide derivatives (AQ4NO and AQ6NO). The drug design rationale was that N-oxide modifications generates prodrug forms suitable for selective bioreductive-activation in hypoxic tumor cells. DNA-binding ranked in the order of mitoxantrone > AQ6 > AQ4 > AQ6NO > AQ4NO. Using both cytometric methods a similar ranking was found for whole cell and nuclear location in human transformed fibroblasts. However, AQ6 showed enhanced nuclear uptake compared with mitoxantrone, in keeping with its greater capacity to inhibit DNA synthesis. Partial charge neutralisation by N-oxide derivatization resulted in loss of DNA synthesis inhibition but retention of the ability to accumulate in the cytosol, an important property for prodrug development. We conclude that both flow cytometry and confocal imaging revealed biologically significant differences between analogues for subcellular distribution and retention properties....Continue Reading

Citations

Oct 10, 2008·The British Journal of Radiology·R L CowenK J Williams
Jun 3, 2008·Nitric Oxide : Biology and Chemistry·Brian FitzpatrickIan J Stratford
Feb 7, 2006·Biochemical Pharmacology·R A AlderdenR Callaghan
Sep 14, 2006·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Kerenza L NjohPaul J Smith
Dec 19, 2002·Cancer Gene Therapy·Helen O McCarthyTracy Robson
Nov 30, 2012·The Journal of Pharmacology and Experimental Therapeutics·Eugene Manley, David J Waxman

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