Induction of the Endoplasmic Reticulum Stress Pathway by Highly Cytotoxic Organoruthenium Schiff-Base Complexes - Archive ouverte HAL Access content directly
Journal Articles Molecular Pharmaceutics Year : 2018

Induction of the Endoplasmic Reticulum Stress Pathway by Highly Cytotoxic Organoruthenium Schiff-Base Complexes

(1) , (2) , (2) , (2) , (3, 4) , (5, 6) , (2, 4)
1
2
3
4
5
6

Abstract

Current anticancer drug discovery efforts focus on the identification of first-in-class compounds with a mode-of-action distinct from conventional DNA-targeting agents for chemotherapy. An emerging trend is the identification of endoplasmic reticulum (ER) targeting compounds that induce ER stress in cancer cells, leading to cell death. However, a limited pool of such compounds has been identified to date, and there are limited studies done on such compounds to allow for the rational design of ER stress-inducing agents. In our present study, we present a series of highly cytotoxic, ER stress-inducing Ru(II)-arene Schiff-Base (RAS) complexes, bearing iminoquinoline chelate ligands. We demonstrate that by structural modification to the iminoquinoline ligand, we could tune its π-acidity and influence reactive oxygen species (ROS) induction, switching between a ROS-mediated ER stress pathway activation and one that is not mediated by ROS induction. Our current study adds to the available ER stress inducers and shows how structural tuning could be used as a means to modulate the mode-of-action of such compounds.
Embargoed file
Embargoed file
Ne sera jamais visible
Loading...

Dates and versions

inserm-02364152 , version 1 (14-11-2019)

Identifiers

Cite

Mun Juinn Chow, Maria Babak, Kwan Wei Tan, Mei Chi Cheong, Giorgia Pastorin, et al.. Induction of the Endoplasmic Reticulum Stress Pathway by Highly Cytotoxic Organoruthenium Schiff-Base Complexes. Molecular Pharmaceutics, 2018, 15 (8), pp.3020-3031. ⟨10.1021/acs.molpharmaceut.8b00003⟩. ⟨inserm-02364152⟩
28 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More