dc.contributor.author |
Pruijn, Frederik |
en |
dc.contributor.author |
Patel, Kashyap |
en |
dc.contributor.author |
Hay, Michael |
en |
dc.contributor.author |
Wilson, William |
en |
dc.contributor.author |
Hicks, Kevin |
en |
dc.date.accessioned |
2012-03-25T19:50:02Z |
en |
dc.date.issued |
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 |
http://hdl.handle.net/2292/15190 |
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 http://www.sherpa.ac.uk/romeo/issn/0004-9425/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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 |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
81298 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |