Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(Rooperol). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Texas State University – San Marcos

1. Bohanon, Amanda. Stability Studies of Rooperol and Analogues by In Vitro Metabolism With HPLC/MS Detection.

Degree: MS, Biochemistry, 2019, Texas State University – San Marcos

African Potato, Hypoxis hemerocallidea, has a long history of use by the indigenous people of South Africa to treat cancer and a variety of other diseases. Extracts from the corm contain the norligan bisglycoside hypoxoside, which is hydrolyzed in the body to yield the anticancer agent rooperol (1,5-bis(3’,4’-dihydroxyphenyl)pent-1-en-4- yne). Studies have shown that rooperol selectively inhibits the growth of several cancer cell lines. Phase I clinical trials of rooperol in lung cancer patients suggested promising activity with no dose-limiting toxicity. However, rooperol is rapidly converted to biologically inactive sulfate and glucuronide metabolites. Thus, a relatively small amount of the drug reaches the tumor site. Bioisosteric analogues of rooperol have been synthesized with the aim of increasing metabolic stability while preserving the anticancer properties of the parent drug. The goal of this research is to investigate the metabolic stability of rooperol and analogues. As part of this study, we employ an in vitro metabolism assay with porcine liver microsomes. Microsomes are supplemented with the cofactor UDP-glucuronic acid and the pore-forming peptide alamethicin. The suitability of this assay to characterize the Phase II metabolism of phenolic compounds was established with the plant phytochemical 3-hydroxytyrosol. The time-dependent metabolism of this compound was determined by HPLC assay, and the formation of the glucuronide Phase II metabolite was confirmed by HPLC/MS. The time course for disappearance of 3-hydroxytyrosol followed first-order kinetics with an apparent half-life of around 61 minutes. We have recently employed this assay to quantify the metabolic lability of rooperol. The disappearance of rooperol monitored by HPLC revealed an exceptionally short half-life of about 3 minutes. The identities of monoglucuronide and diglucuronide metabolites of rooperol were verified by HPLC/MS. The extreme metabolic lability of rooperol demonstrates the need to identify more metabolically stable analogues. We will discuss the integration of this in vitro metabolism assay in a work- flow designed to identify rooperol analogues exhibiting increased metabolic stability while retaining the cytotoxic activity of rooperol. Advisors/Committee Members: Kerwin, Sean M. (advisor), David, Wendi (committee member), Du, Liqin (committee member).

Subjects/Keywords: Rooperol; Hydroxytyrosol; Glucuronidation; In vitro; Metabolism; HPLC/MS

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bohanon, A. (2019). Stability Studies of Rooperol and Analogues by In Vitro Metabolism With HPLC/MS Detection. (Masters Thesis). Texas State University – San Marcos. Retrieved from https://digital.library.txstate.edu/handle/10877/8179

Chicago Manual of Style (16th Edition):

Bohanon, Amanda. “Stability Studies of Rooperol and Analogues by In Vitro Metabolism With HPLC/MS Detection.” 2019. Masters Thesis, Texas State University – San Marcos. Accessed May 25, 2019. https://digital.library.txstate.edu/handle/10877/8179.

MLA Handbook (7th Edition):

Bohanon, Amanda. “Stability Studies of Rooperol and Analogues by In Vitro Metabolism With HPLC/MS Detection.” 2019. Web. 25 May 2019.

Vancouver:

Bohanon A. Stability Studies of Rooperol and Analogues by In Vitro Metabolism With HPLC/MS Detection. [Internet] [Masters thesis]. Texas State University – San Marcos; 2019. [cited 2019 May 25]. Available from: https://digital.library.txstate.edu/handle/10877/8179.

Council of Science Editors:

Bohanon A. Stability Studies of Rooperol and Analogues by In Vitro Metabolism With HPLC/MS Detection. [Masters Thesis]. Texas State University – San Marcos; 2019. Available from: https://digital.library.txstate.edu/handle/10877/8179

2. -6306-7187. Synthesis of isosteric analogues of rooperol.

Degree: Pharmaceutical Sciences, 2017, University of Texas – Austin

Hypoxoside is a norlignan bisglycoside derived from Hypoxis hemerocallidae (African potato), a medicinal plant used in Africa to treat a variety of disorders, including cancer, cardiac diseases, immune disfunction, inflammation, and prostate hyperplasia. Its aglycone form, (1,5-bis(3’,4’-dihydroxyphenyl)pent-1-en-4-yne (rooperol) is produced in the presence of β-glucosidase which is present in the GI lumen, leading investigators to evaluate hypososide as a potential oral prodrug. Unfortunately, the presence of catechol moieties results in extensive phase II metabolism before therapeutic blood concentrations are achieved. One approach to address this obstacle is to replace the catechols with isosteres which may be more metabolically stable and possess the same bioactivity. This body of work is focused on the synthesis of rooperol and three analogues of rooperol of which the catechol moieties are replaced with a small set of isosteres. Advisors/Committee Members: Whitman, Christian P. (advisor), Fast, Walter L. (advisor).

Subjects/Keywords: Rooperol; Hypoxoside; Catechol; Natural products; Glucosides; Prodrug

…extracts (rooperol and stigmasterol) on some cellular pathways so far investigated… …constituent is hypoxoside. OH a. OH OH OH diphenyl-1-en-4-yne-pentane skeleton (rooperol… …structures of rooperol and hypoxoside Early work evaluating the therapeutic effects of hypoxoside… …to the aglycone.19,20 Drewes et al. named this aglycone rooperol (Figure 1.2.1a)… …hypoxoside and rooperol toward B16-F10-BL-6 mouse melanoma cells, as well as demonstrated the… 

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

-6306-7187. (2017). Synthesis of isosteric analogues of rooperol. (Thesis). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/47298

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

-6306-7187. “Synthesis of isosteric analogues of rooperol.” 2017. Thesis, University of Texas – Austin. Accessed May 25, 2019. http://hdl.handle.net/2152/47298.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

-6306-7187. “Synthesis of isosteric analogues of rooperol.” 2017. Web. 25 May 2019.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

-6306-7187. Synthesis of isosteric analogues of rooperol. [Internet] [Thesis]. University of Texas – Austin; 2017. [cited 2019 May 25]. Available from: http://hdl.handle.net/2152/47298.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

-6306-7187. Synthesis of isosteric analogues of rooperol. [Thesis]. University of Texas – Austin; 2017. Available from: http://hdl.handle.net/2152/47298

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

3. Ali-Azouaou, Sarah. Evaluation des effets anticancéreux de composés pharmacologiques sur les cellules souches cancéreuses et leurs descendants : caractérisation des mécanismes moléculaires : Anticancer effects of pharmacological compounds on cancer stem cells and their descendants : characterization of the molecular mechanisms involved.

Degree: Docteur es, Pharmacologie, 2015, Université de Strasbourg

Les cellules souches cancéreuses (CSCs) représentent une petite sous-population de cellules dans la tumeur qui sont capables de s'autorenouveler. Ce sont des cellules impliquées dans l'initiation et la croissance métastasique des tumeurs, ainsi que dans la résistance aux traitements conventionnels. Ces CSCs expriment les facteurs de pluripotence Oct4, Nanog et Sox2, lorsqu’elles sont fortement indifférenciées. Mon travail de thèse a consisté à analyser les effets anticancéreux de produits phytochimiques sur des CSCs. Nous avons ainsi étudié l’activité anti-carcinogénique sélective du roopérol sur un modèle de CSC tératocarcinomale. Le roopérol entraîne un processus pro-apoptotique et induit l’activation de la p53 et de la caspase 3, via la formation intracellulaire d'espèces réactives d’oxygène (ERO), ce qui conduit à une chute de l'expression d’Oct4 et Nanog. Un tel effet n’est pas observé dans les cellules souches normales (CSNs). Nous avons donc étudié le mécanisme impliqué dans la résistance des CSNs au traitement par le roopérol. Ce dernier n'y provoque aucune formation de ERO, mais active sélectivement les protéines de pro-survie Akt et Bad. Dans une 2eme étude, nous avons examiné le potentiel anticancéreux sélectif de plusieurs dérivés triterpéniques de type avicine, issus de différentes espèces d’Albizzia africaines, sur un modèle de carcinome épidermoïde. Après criblage, nous avons choisi d'étudier plus en profondeur les mécanismes moléculaires mis en jeu par le composé qui présentait la plus grande activité pro-apoptotique. Cette analyse a été effectuée dans un modèle de mélanome métastasique agressif connu pour exprimer Oct4. Nous démontrons que l'agent pharmacologique entraîne une apoptose sélective des cellules de mélanome, via une activation de la p38 MAPK et de la caspase 3, suivie d’une diminution de l’expression d’Oct4. Un tel effet apoptotique n’a pas été observé dans les cellules normales. Ces résultats permettent ainsi de mettre en évidence de nouveaux et puissants composés anticancéreux, capables d’induire sélectivement et in vitro l’apoptose des CSCs et leurs descendants, tout en épargnant les CSNs et leurs descendants.

Cancer stem cells (CSCs) are a small subpopulation of cells in the tumor which are able to self-renew. These cells are involved in the initiation and the metastatic growth of tumors, as well as in the resistance to conventional treatments. In their highly undifferentiated state, CSCs are known to express the stemness factors Oct4 and Nanog. The aim of this work was therefore to analyze the effects of phytochemicals on Oct-4 expressing teratocarcinomal stem-like cells. In a first study, we investigated the selective anti-carcinogenic activity of rooperol, the aglycone of the plant-derived compound hypoxoside. We observed that the rooperol-induced apoptosis in CSCs was associated with an oxidative stress, dependent of the activation of p53 and cleaved caspase 3 expression. These modifications were accompanied by reduced expression of the stemness factors. Such effect was however…

Advisors/Committee Members: Muller, Christian D. (thesis director), Lobstein, Annelise (thesis director).

Subjects/Keywords: Cellule souche cancéreuse; Apoptose; Oct4; Roopérol; Dérivés triterpéniques de type avicine; Cancer stem cells; Apoptosis; Oct4; Rooperol; Acacic acid-type saponins; 615.7

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Ali-Azouaou, S. (2015). Evaluation des effets anticancéreux de composés pharmacologiques sur les cellules souches cancéreuses et leurs descendants : caractérisation des mécanismes moléculaires : Anticancer effects of pharmacological compounds on cancer stem cells and their descendants : characterization of the molecular mechanisms involved. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2015STRAJ087

Chicago Manual of Style (16th Edition):

Ali-Azouaou, Sarah. “Evaluation des effets anticancéreux de composés pharmacologiques sur les cellules souches cancéreuses et leurs descendants : caractérisation des mécanismes moléculaires : Anticancer effects of pharmacological compounds on cancer stem cells and their descendants : characterization of the molecular mechanisms involved.” 2015. Doctoral Dissertation, Université de Strasbourg. Accessed May 25, 2019. http://www.theses.fr/2015STRAJ087.

MLA Handbook (7th Edition):

Ali-Azouaou, Sarah. “Evaluation des effets anticancéreux de composés pharmacologiques sur les cellules souches cancéreuses et leurs descendants : caractérisation des mécanismes moléculaires : Anticancer effects of pharmacological compounds on cancer stem cells and their descendants : characterization of the molecular mechanisms involved.” 2015. Web. 25 May 2019.

Vancouver:

Ali-Azouaou S. Evaluation des effets anticancéreux de composés pharmacologiques sur les cellules souches cancéreuses et leurs descendants : caractérisation des mécanismes moléculaires : Anticancer effects of pharmacological compounds on cancer stem cells and their descendants : characterization of the molecular mechanisms involved. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2015. [cited 2019 May 25]. Available from: http://www.theses.fr/2015STRAJ087.

Council of Science Editors:

Ali-Azouaou S. Evaluation des effets anticancéreux de composés pharmacologiques sur les cellules souches cancéreuses et leurs descendants : caractérisation des mécanismes moléculaires : Anticancer effects of pharmacological compounds on cancer stem cells and their descendants : characterization of the molecular mechanisms involved. [Doctoral Dissertation]. Université de Strasbourg; 2015. Available from: http://www.theses.fr/2015STRAJ087

.