Open AccessExpeditive Synthesis of Potent C20-epi-Amino Derivatives of Salinomycin against Cancer Stem-Like Cells
Author(s) -
Dominika Czerwonka,
Sebastian Müller,
Tatiana Cañeque,
Ludovic Colombeau,
Adam Huczyński,
Michał Antoszczak,
Raphaël Rodriguez
Publication year - 2022
Publication title -
acs organic and inorganic au
Language(s) - English
Resource type - Journals
ISSN - 2694-247X
DOI - 10.1021/acsorginorgau.1c00046
Subject(s) - salinomycin , cancer stem cell , ionophore , mesenchymal stem cell , chemistry , amine gas treating , stem cell , cell culture , small molecule , stereochemistry , mcf 7 , cancer cell , cancer research , combinatorial chemistry , biochemistry , cancer , biology , human breast , microbiology and biotechnology , organic chemistry , genetics , membrane , antibiotics
As a continuation of our studies toward the development of small molecules to selectively target cancer stem cells (CSCs), a library of 18 novel derivatives of salinomycin ( Sal ), a naturally occurring polyether ionophore, was synthesized with a good overall yield using a one-pot Mitsunobu-Staudinger procedure. Compared to the parent structure, the newly synthesized products contained the mono- or disubstituted C20- epi -amine groups. The biological activity of these compounds was evaluated against human mammary mesenchymal HMLER CD24 low /CD44 high cells, a well-established model of breast CSCs, and its isogenic epithelial cell line (HMLER CD24 high /CD44 low ) lacking CSC properties. Importantly, the vast majority of Sal derivatives were characterized by low nanomolar activities, comparing favorably with previous data in the literature. Furthermore, some of these derivatives exhibited a higher selectivity for the mesenchymal state compared to the reference Sal and ironomycin, representing a promising new series of compounds with anti-CSC activity.