Open AccessTurning a Quinoline-based Steroidal Anticancer Agent into Fluorescent Dye for its Tracking by Cell Imaging
Author(s) -
René Maltais,
Jenny Roy,
Donald Poirier
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.1c00111
Subject(s) - quinoline , fluorescence , endoplasmic reticulum , colocalization , confocal , chemistry , cytotoxic t cell , confocal microscopy , fluorescence microscope , cancer cell , cell , biophysics , biochemistry , cancer , microbiology and biotechnology , biology , in vitro , organic chemistry , physics , geometry , mathematics , genetics , quantum mechanics
RM-581 is an aminosteroid derivative comprised of a steroid core and a quinoline side chain showing potent cytotoxic activity on several types of cancer cells but for which the mechanism of action (MoA) remains to be fully elucidated. The opportunity to turn RM-581 into a fluorescent probe was explored because the addition of a N -dimethyl group was recently reported to induce fluorescence to quinoline derivatives. After the chemical synthesis of the N -dimethyl analogue of RM-581 (RM-581-Fluo), its fluorescent properties, as well as its cytotoxic activity in breast cancer MCF-7 cells, were confirmed. A cell imaging experiment in MCF-7 cells using confocal microscopy then revealed that RM-581-Fluo accumulated into the endoplasmic reticulum (ER) as highlighted by its colocalization with an ER-Tracker dye. This work provides a new tool for RM-581 MoA investigations as well as being a relevant example of a tailor-made quinolone-fluorescent version of a bioactive molecule.