dc.contributor.author |
Rewcastle, Gordon |
en |
dc.contributor.author |
Atwell, Graham |
en |
dc.contributor.author |
Baguley, Bruce |
en |
dc.contributor.author |
Boyd, Maruta |
en |
dc.contributor.author |
Thomsen, LL |
en |
dc.contributor.author |
Zhuang, L |
en |
dc.contributor.author |
Denny, William |
en |
dc.coverage.spatial |
UNITED STATES |
en |
dc.date.accessioned |
2012-03-21T00:24:20Z |
en |
dc.date.issued |
1991 |
en |
dc.identifier.citation |
ournal of Medicinal Chemistry 34(9):2864-2870 1991 |
en |
dc.identifier.issn |
0022-2623 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/14879 |
en |
dc.description.abstract |
A series of 16 analogues of the solid tumor active compound 9-0~0-9H-xanthene-4-acetic acid (XAA), with variations in the acetic acid side chain, have been prepared and evaluated for their ability to cause early haemorrhagic necrosis of colon 38 tumors in mice. The results extend the previous S A R for this class and confirm the necessity for a carboxylic acid group in a fixed disposition with respect to the xanthenone chromophore. None of the compounds showed superior potency to XAA itself, with virtually all alterations in the nature of the anionic center or its geometry with respect to the chromophore greatly reducing or abolishing activity. However, a-methylation of the side chain was permissible, and the two enantiomers of 5-methyl-a-methyl-XAA were separated and tested. Both were active, but the S-(+) enantiomer was much more dose-potent than the I?-(--) enantiomer, in both the in vivo tumor necrosis assay and an in vitro assay measuring the stimulation of nitric oxide production by macrophages. This suggests that the enantiomers have different intrinsic activities, rather than differing in their vivo metabolism. |
en |
dc.language |
eng |
en |
dc.publisher |
American Chemical Society |
en |
dc.relation.ispartofseries |
Journal of Medicinal 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/0022-2623/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Animals |
en |
dc.subject |
Antineoplastic Agents |
en |
dc.subject |
Colonic Neoplasms |
en |
dc.subject |
Drug Screening Assays, Antitumor |
en |
dc.subject |
Macrophages |
en |
dc.subject |
Methylation |
en |
dc.subject |
Mice |
en |
dc.subject |
Nitrates |
en |
dc.subject |
Nitrites |
en |
dc.subject |
Structure-Activity Relationship |
en |
dc.subject |
Xanthenes |
en |
dc.title |
Potential antitumor agents. 63. Structure-activity relationships for side-chain analogues of the colon 38 active agent 9-oxo-9H-xanthene-4-acetic acid |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1021/jm00113a027 |
en |
pubs.issue |
9 |
en |
pubs.begin-page |
2864 |
en |
pubs.volume |
34 |
en |
dc.rights.holder |
Copyright: American Chemical Society |
en |
dc.identifier.pmid |
1895304 |
en |
pubs.end-page |
2870 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
130413 |
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 |
2012-08-06 |
en |
pubs.dimensions-id |
1895304 |
en |