Synthesis, Characterization, and Biological Properties of Osmium-Based Tamoxifen Derivatives - Comparison with Their Homologues in the Iron and Ruthenium Series

Three osmium analogues 3a–3c of hydroxytamoxifen were prepared. The antiproliferative effects of these complexes were measured against two breast cancer cell lines (MCF-7 and MDA-MB-231) and compared with those of their homologues of ferrocene (1a–1c) and ruthenocene (2a–2c). The tamoxifen-like comp...

Full description

Saved in:
Bibliographic Details
Main Authors: Lee, Hui Zhi Shirley, Buriez, Olivier, Chau, François, Labbé, Eric, Ganguly, Rakesh, Amatore, Christian, Jaouen, Gérard, Vessières, Anne, Leong, Weng Kee, Top, Siden
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2015
Subjects:
Online Access:https://hdl.handle.net/10356/103650
http://hdl.handle.net/10220/38791
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
Description
Summary:Three osmium analogues 3a–3c of hydroxytamoxifen were prepared. The antiproliferative effects of these complexes were measured against two breast cancer cell lines (MCF-7 and MDA-MB-231) and compared with those of their homologues of ferrocene (1a–1c) and ruthenocene (2a–2c). The tamoxifen-like complexes 2c and 3c derived from osmium and ruthenium show good cytotoxicities against the two cell lines (IC50 values between 2 and 3 μM), albeit lower than those of ferrocifen 1c (IC50 between 0.5 and 0.8 μM). These complexes induce senescence of the cells at low concentration (0.5 μM). The mono- and diphenol complexes of osmium and ruthenium show little cytotoxicity against the two cell lines (2a, 2b, 3a, 3b; IC50 ≈ 30 μM), whereas the iron analogues show high cytotoxicity (1a and 1b; IC50 = 0.6–1.1 μM against MDA-MB-231). Further studies show that the cytotoxicity of the tamoxifen-like complexes of ruthenium and osmium is multifactorial and is partly due to the presence of the amino chain. Added to this is an effect of the metal center that could be due to a difference in the rate of formation, solubility, and stability of the corresponding quinone methides or to a difference in the acidity of the phenol protons. This work reveals the differences in the mechanisms of action that exist among the complexes of these three metallocenes. The uniqueness of the ferrocene complexes is underlined, but the cytotoxicity of the tamoxifen-like complexes of osmium and ruthenium is also demonstrated.