Biological activity of doubly modified salinomycin analogs - Evaluation in vitro and ex vivo

European Journal of Medicinal Chemistry
Michał AntoszczakDaniel Strand

Abstract

The polyether ionophore salinomycin has recently captured much interest due to its potent activity against multi-drug resistant cancer cells and cancer stem cells. Previous studies have shown that either acylation of the C20 position or esterification/amidation of the C1 carboxylate moiety is beneficial in terms of biological properties. In this paper, we present the first analogs combining such modifications. Evaluation of the anti-proliferative activity against a series of cancer cell lines showed that acylation of the C20 hydroxyl group improves the activity of salinomycin C1 amides but not of the corresponding C1 esters. Importantly, the activity of several of the doubly modified analogs surpasses that of commonly used cytostatic drugs cisplatin and doxorubicin in the LoVo/DX multi-drug resistant cell line. All analogs were tested against primary acute lymphoblastic leukemia cells in standard cell viability assays; three were more potent than salinomycin. Further studies revealed that selected analogs induced characteristics of apoptotic cell death and increased expression of p53. Additionally, using an ex vivo model of breast tumor, tumor cell viability significantly decreased after treatment with salinomycin or its double...Continue Reading

Citations

Sep 29, 2018·Cancers·Vivek KaushikAnand K V Iyer
Apr 15, 2020·Cellular and Molecular Life Sciences : CMLS·D ContarteseM Fini
Jul 16, 2020·Biomolecules·Michał SulikMichał Antoszczak
Jan 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marcin MichalakWiktoria Maria Suchorska
Dec 22, 2020·European Journal of Pharmacology·Dominika KuranAdam Huczyński
Jan 29, 2019·Journal of the American Chemical Society·Fengfei WangErxi Wu
Jun 16, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Alicja UrbaniakAngus M MacNicol
Jul 16, 2021·European Journal of Pharmacology·Dominika CzerwonkaAdam Huczyński
Dec 4, 2020·European Journal of Pharmacology·Alicja UrbaniakTimothy C Chambers

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