dc.contributor.author |
Mothibeli, K.T.
|
|
dc.contributor.author |
Mercier, Anne Elisabeth
|
|
dc.contributor.author |
Cromarty, Allan Duncan
|
|
dc.contributor.author |
Rheeder, M.
|
|
dc.contributor.author |
Naidoo, Vinny
|
|
dc.contributor.author |
Olorunju, S.A.S.
|
|
dc.contributor.author |
Joubert, Anna Margaretha
|
|
dc.date.accessioned |
2019-02-04T09:12:52Z |
|
dc.date.available |
2019-02-04T09:12:52Z |
|
dc.date.issued |
2018 |
|
dc.description.abstract |
2-methoxyestradiol (2ME) is an endogenous 17β-oestradiol metabolite that exerts antiproliferative,
antiangiogenic and antitumour activity on cancer cells both in vitro and in vivo. However, the use of
2ME as a potential anticancer agent is limited due to its poor oral bioavailability coupled to a short
elimination half-life. In an attempt to improve the oral bioavailability and expand the drug targets, three
sulphamoylated 2ME analogues were designed using in silico modelling and subsequently synthesized. A
screening limit of 5 μg/ml for each analogue using a liquid chromatography tandem mass spectrometer
(LC-MS/MS) method for 2ME analogues in serum and solvent was established. Therapeutically relevant
oral bioavailability was assessed for these 2ME analogues using a murine oral absorption model (CD-1
mice) where the presence of these synthetic analogues in serum samples was assessed at two hours post
dosing at 150 mg/kg of individual compounds. Blood was collected and analysed for the presence of the
dosed compound and potential metabolites via LC-MS/MS. Results indicated that these analogues were
present in serum above the screening limit at two hours post dosing and that there is merit to further
investigation into the mode and mechanism(s) of action of ESE-15-one and ESE-15-ol and ESE-16 in
vivo. |
en_ZA |
dc.description.department |
Pharmacology |
en_ZA |
dc.description.department |
Physiology |
en_ZA |
dc.description.librarian |
am2019 |
en_ZA |
dc.description.sponsorship |
Grants from the Cancer
Association of South Africa (A0V741, A0W228, A0B741), the
Struwig Germeshuysen Trust (A0N074), Research Committee,
School of Medicine (University of Pretoria) (A0H561),
National Research Foundation (N00375, N00591) and the
Medical Research Council (A0W110) awarded to Prof. AM
Joubert. The mass spectrometers used in this study were both
purchased with financial support from the National Research
Foundation. |
en_ZA |
dc.description.uri |
http://www.alliedacademies.org/biomedical-research |
en_ZA |
dc.identifier.citation |
Mothibeli, K.T., Mercier, A.E., Cromarty, A.D. et al. 2018, 'Confirming oral bioavailability of novel oestradiol analogues by liquid
chromatography-tandem mass spectrometry in a murine model', Biomedical Research, vol. 29, no. 17, pp. 3267-3275. |
en_ZA |
dc.identifier.issn |
0388-6107 (print) |
|
dc.identifier.issn |
1880-313X (online) |
|
dc.identifier.other |
10.4066/biomedicalresearch.29-17-2838 |
|
dc.identifier.uri |
http://hdl.handle.net/2263/68380 |
|
dc.language.iso |
en |
en_ZA |
dc.publisher |
Allied Academies |
en_ZA |
dc.rights |
© Allied Academies 2018. Creative Commons License Open Access Journals by Allied Academies is licensed under a Creative Commons Attritbution 4.0 International License. |
en_ZA |
dc.subject |
Oral bioavailability |
en_ZA |
dc.subject |
Murine |
en_ZA |
dc.subject |
2-methoxyestradiol (2ME) |
en_ZA |
dc.subject |
Liquid chromatography tandem mass spectrometer (LC-MS/MS) |
en_ZA |
dc.title |
Confirming oral bioavailability of novel oestradiol analogues by liquid chromatography-tandem mass spectrometry in a murine model |
en_ZA |
dc.type |
Article |
en_ZA |