Turning a Quinoline-based Steroidal Anticancer Agent into Fluorescent Dye for its Tracking by Cell Imaging

Abstract

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.

Induction of Endoplasmic Reticulum Stress-Mediated Apoptosis by Aminosteroid RM-581 Efficiently Blocks the Growth of PC-3 Cancer Cells and Tumors Resistant or Not to Docetaxel

“…EC 50 values of the fluorescent version of RM-581 (RM-581-Fluo) were also compared in PC-3 cells (1.1 and 4.5 µM, respectively) and were relatively close to each other ( Figure 1 ). Considering their similar molecular structure, physicochemical and ADME properties ( Tables S1 and S2, Supplementary Materials ), and cytotoxic activity in PC-3 and MCF-7 cell lines, RM-581-Fluo is a valuable probe of RM-581 [ 34 ].…”

“…RM-581-Fluo is a fluorescent dye of RM-581 that was successfully used in MCF-7 cell imaging [ 34 ]. Having this unique tool in hand, we studied the distribution of RM-581 in PC-3 cells.…”

“…Aminosteroid RM-581 and RM-581-Fluo were prepared as previously reported, and their purity was determined by high-performance liquid chromatography as 99.6% and 91.6%, respectively [ 20 , 34 ].…”

Synthesis, Photophysical Properties, Theoretical Studies, and Living Cancer Cell Imaging Applications of New 7-(Diethylamino)quinolone Chalcones

“…17 Even more the relevance of the incorporation of dialkylamino groups in the quinolone moiety has been assessed on its key effect on the photophysical properties, 18 such as UV−vis spectra (causing a red shift), Stokes shift, and fluorescence quantum yield, generating high efficient materials in the electron transport, high photoluminescence efficiencies, and biological imaging properties. 19 In addition, quinolones have exhibited interesting biological properties, such as antimicrobial, 20 antifungal, 21 antiviral, 22 antimalarial, 23 antituberculosis, 24 antioxidant, 25 and anticancer. 26 On the other hand, chalcones are a class of organic compounds that contain a central α,β-unsaturated carbonyl system, which has attracted significant attention, 27 due to their diverse applications in the fields of medicine, 26 material science, and optics.…”

Superoxide targeted “turn-on” fluorescence sensing enabled by a diselenide based quinoline probe and its in vitro anticancer activity in cancer cells

“…There are many quinoline based anticancer agents reported in the literature; hence, there is a need to check the biological properties of this type of compound. 24,25 As we know, many fluorophore derivatives such as BODIPY, fluorescein, dibenzothiazoline and cyclohexene have been synthesized for detection of superoxide ions; however, there is only one report on quinoline based derivatives. [26][27][28][29][30] Also, there are many reports on organoselenium containing fluorescent probes for the detection of superoxide and their utility for live cell imaging.…”