Composés organometalliques d'osmium pour la thérapie du cancer

Organometallic compounds of osmium for cancer therapy

• Auteur / Autrice : Hui Zhi Shirley Lee
• Direction : Siden Top
• Type : Thèse de doctorat
• Discipline(s) : Chimie
• Date : Soutenance en 2015
• Etablissement(s) : Palaiseau, Ecole polytechnique

Mots clés

Mots clés contrôlés

Chimie pharmaceutique

Cancer du sein

Anticancéreux

Osmium

Mots clés libres

Bioorganometallique

Osmocène

Résumé

Cis-platin and its derivatives are the most currently used for cancer treatment. Inspired by these metallodrugs, organometallic compounds (Ti, Ru, Fe, Rh, Au…) have been developed over the years as potential candidates for anticancer drugs, some of these have entered clinical trials. Jaouen and co-workers have developed novel therapeutic agents based on ferrocene compounds analogous to tamoxifen, which show high anti-proliferative effects against two types of breast cancer cells, namely the ER+ breast carcinoma (MCF-7) and the ER- breast carcinoma (MDA-MB-231). Similarly, Leong’s group has found a series of triosmium carbonyl clusters that shows anticancer activity against these two breast cancer cells. Thus, it would be interesting to study osmocene compounds analogous to tamoxifen. Cytotoxic activity of these tamoxifen analogues, as well as that of triosmium clusters, were studied. This work aims to study the relationship between structure and activity of triosmium cluster Os3(CO)10(NCMe)2 compound with cytotoxic properties. The results show that the presence of a vacant coordination site and good solubility are important to have a good cytotoxic activity. The second part of the study was devoted to osmocene analogues (osmocifens), especially in the comparative study between the cytotoxic activity of three metallocene series: ferrocifen, ruthenocifen and osmocen. For osmium and ruthenium complexes, only compounds containing the amino chain are active while the phenolic compounds are almost inactive.