Skip to Main content Skip to Navigation
Theses

Synthèse de nouveaux phosphinosucres et pseudo-disaccharides à activité anticancéreuse

Abstract : The Phostines represent a new class of glycomimetics, containing a phosphinolactone function instead of the anomeric carbon. Their synthesis was achieved by the reaction of protected furanose with various H-phosphinates, in the presence of a base. These compounds have been found to be very effective in vitro and in vivo against rat and human glioblastoma cells.In this project, our first goal was to obtain the most active phostine with higher diastereoselectivity. Different reactions were tested, changing the base or its counter ion. A very slight improvement was noted with cesium methoxide, favoring the glucose-like derivative.In the context of improving the anticancer activity and to study the biodistribution of the phostines, different chemical modifications were carried out. Dihydroxy-2,3- and 2,6-oxaphosphinanes, thiophostines and phostines of the L series were synthesized. Therefore, variations in alpha position of the phosphorus atom have produced halogenated phostines and two new products: furanosylphosphinic acid and the oxaphosphine-3-ene.The chemical reactivity of the enol ether of this latter has been examined by synthesizing beta-ketophosphinate and beta-enaminophosphinates. Finally, pseudo-disaccharides were synthesized to improve the bioavailability of phostines.The tested phostines have exhibited anticancer properties at nanomolar concentration against different cell lines, showing the ability of this family of compounds to fight some types of cancers.
Document type :
Theses
Complete list of metadatas

Cited literature [167 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01755214
Contributor : Abes Star :  Contact
Submitted on : Friday, March 30, 2018 - 2:36:07 PM
Last modification on : Wednesday, October 14, 2020 - 4:08:58 AM

File

2016_BABOURI_archivage.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01755214, version 1

Collections

Citation

Rachida Babouri. Synthèse de nouveaux phosphinosucres et pseudo-disaccharides à activité anticancéreuse. Ingénierie biomédicale. Université Montpellier; Université Mentouri-Constantine, 2016. Français. ⟨NNT : 2016MONTT191⟩. ⟨tel-01755214⟩

Share

Metrics

Record views

335

Files downloads

388