Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 12, Issue 5, Pages 822-826Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.1c00111
Keywords
Fluorophore; cell imaging; quinoline; steroid; anticancer agent; breast cancer
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Funding
- Ministere de l'economie et de l'innovation (MEI) du Quebec.Programme de soutien aux organismes de recherche et d'innovation (PSO-2D-validation medicament)
- Societe de valorisation des applications de la recherche (SOVAR)
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RM-581, a potent aminosteroid derivative with cytotoxic activity against cancer cells, was modified to create a fluorescent probe RM-581-Fluo, which was found to accumulate in the endoplasmic reticulum of breast cancer cells, providing a new tool for investigating its mechanism of action.
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.
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