dc.contributor.author |
Zafar, Ayesha |
en |
dc.contributor.author |
Pilkington, Lisa |
en |
dc.contributor.author |
Haverkate, Natalie |
en |
dc.contributor.author |
van Rensburg, Michelle |
en |
dc.contributor.author |
Leung, Yee Fun |
en |
dc.contributor.author |
Kumara, Sisira |
en |
dc.contributor.author |
Denny, William |
en |
dc.contributor.author |
Barker, David |
en |
dc.contributor.author |
Alsuraifi, Ali |
en |
dc.contributor.author |
Hoskins, Clare |
en |
dc.contributor.author |
Reynisson, Johannes |
en |
dc.date.accessioned |
2018-11-27T02:48:28Z |
en |
dc.date.issued |
2018-01-11 |
en |
dc.identifier.citation |
Molecules 23(1) 11 Jan 2018 |
en |
dc.identifier.issn |
1420-3049 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/44634 |
en |
dc.description.abstract |
It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategies were pursued. First, a morpholine moiety was tethered to the molecular scaffold by substituting the sulphur atom with nitrogen, resulting in a 1H-pyrrolo[2,3-b]pyridine core structure. The water solubility was increased by three orders of magnitude, from 1.2 µg/mL (1-thieno[2,3-b]pyridine) to 1.3 mg/mL (3-pyrrolo[2,3-b]pyridine), however, it was only marginally active against cancer cells. The second strategy involved loading a very potent thieno[2,3-b]pyridine derivative (2) into a cholesteryl-poly(allylamine) polymer matrix for water solubilisation. Suppression of human pancreatic adenocarcinoma (BxPC-3) viability was observed to an IC50 value of 0.5 μg/mL (1.30 μM) in conjunction with the polymer, which is a five-fold (×5) increase in potency as compared to the free drug alone, demonstrating the utility of this formulation approach. |
en |
dc.format.medium |
Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Molecules (Basel, Switzerland) |
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. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
en |
dc.subject |
Cell Line, Tumor |
en |
dc.subject |
Humans |
en |
dc.subject |
Pyridines |
en |
dc.subject |
Polymers |
en |
dc.subject |
Antineoplastic Agents |
en |
dc.subject |
Cell Proliferation |
en |
dc.subject |
Molecular Structure |
en |
dc.subject |
Molecular Conformation |
en |
dc.subject |
Structure-Activity Relationship |
en |
dc.subject |
Solubility |
en |
dc.subject |
Models, Molecular |
en |
dc.title |
Investigation into Improving the Aqueous Solubility of the Thieno[2,3-b]pyridine Anti-Proliferative Agents. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.3390/molecules23010145 |
en |
pubs.issue |
1 |
en |
pubs.volume |
23 |
en |
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
29324695 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
721745 |
en |
pubs.org-id |
Academic Services |
en |
pubs.org-id |
Examinations |
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 |
Chemistry |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1420-3049 |
en |
pubs.record-created-at-source-date |
2018-01-12 |
en |
pubs.dimensions-id |
29324695 |
en |