Prediction of Tumour Tissue Diffusion Coefficients of Hypoxia-Activated Prodrugs from Physicochemical Parameters

Show simple item record Pruijn, Frederik en Patel, Kashyap en Hay, Michael en Wilson, William en Hicks, Kevin en 2012-03-25T19:50:02Z en 2008 en
dc.identifier.citation Australian Journal of Chemistry 61(9):687-693 01 Jan 2008 en
dc.identifier.issn 0004-9425 en
dc.identifier.uri en
dc.description.abstract The therapeutic activity of anticancer agents depends critically on their ability to penetrate through tumour tissue to reach their target cells, a requirement that is especially important for hypoxia-activated prodrugs. Here we use multicellular layers (MCL) grown in vitro from HT29 colon carcinoma cells to measure tissue diffusion coefficients (Dmcl) of 67 structurally diverse benzotriazine di-N-oxides (analogues of the hypoxia-activated prodrug tirapazamine) plus four miscellaneous compounds.An algorithm was developed to predict Dmcl from physicochemical parameters (molecular weight, octanol/water partition coefficient at pH 7.4, number of hydrogen bond donors and acceptors); the fitted multivariate relationship had an explained variance (R2) of 0.907 and predictive power (Q2) of 0.879. Using a subset of nine compounds tested as a single cassette, the algorithm was shown to apply, with some adjustment of coefficients, to MCLs from three other tumour cell lines with differing cell packing densities (SiHa, HCT8-Ea, and HCT8-Ra). The demonstrated relationships provide tools for optimizing extravascular transport of anticancer agents during lead optimization. en
dc.publisher CSIRO Publishing en
dc.relation.ispartofseries Australian Journal of Chemistry en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.title Prediction of Tumour Tissue Diffusion Coefficients of Hypoxia-Activated Prodrugs from Physicochemical Parameters en
dc.type Journal Article en
dc.identifier.doi 10.1071/CH08240 en
pubs.issue 9 en
pubs.begin-page 687 en
pubs.volume 61 en
dc.rights.holder Copyright: CSIRO Publishing en
pubs.end-page 693 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 81298 en Medical and Health Sciences en Medical Sciences en Auckland Cancer Research en Science en Science Research en Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2010-09-01 en

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