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Synthesis and Anticancer Activity of Tertiary Amides of Salinomycin and Their C20-oxo Analogues.

Publication ,  Journal Article
Czerwonka, D; Urbaniak, A; Sobczak, S; Piña-Oviedo, S; Chambers, TC; Antoszczak, M; Huczyński, A
Published in: ChemMedChem
January 17, 2020

The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, herein we describe the synthesis of a new class of SAL analogues that combine key modifications at the C1 and C20 positions. The activity of the obtained SAL derivatives was evaluated using primary acute lymphoblastic leukemia, human breast adenocarcinoma and normal mammary epithelial cells. One single- [N,N-dipropyl amide of salinomycin (5 a)] and two novel double-modified analogues [N,N-dipropyl amide of C20-oxosalinomycin (5 b) and piperazine amide of C20-oxosalinomycin (13 b)] were found to be more potent toward the MDA-MB-231 cell line than SAL or its C20-oxo analogue 2. When select analogues were tested against the NCI-60 human tumor cell line panel, 4 a [N,N-diethyl amide of salinomycin] showed particular activity toward the ovarian cancer cell line SK-OV-3. Additionally, both SAL and 2 were found to be potent ex vivo against human ER/PR+ , Her2- invasive mammary carcinoma, with 2 showing minimal toxicity toward normal epithelial cells. The present findings highlight the therapeutic potential of SAL derivatives for select targeting of different cancer types.

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Published In

ChemMedChem

DOI

EISSN

1860-7187

Publication Date

January 17, 2020

Volume

15

Issue

2

Start / End Page

236 / 246

Location

Germany

Related Subject Headings

  • Structure-Activity Relationship
  • Pyrans
  • Molecular Conformation
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Drug Screening Assays, Antitumor
  • Dose-Response Relationship, Drug
  • Cells, Cultured
  • Cell Survival
  • Cell Proliferation
 

Citation

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Czerwonka, D., Urbaniak, A., Sobczak, S., Piña-Oviedo, S., Chambers, T. C., Antoszczak, M., & Huczyński, A. (2020). Synthesis and Anticancer Activity of Tertiary Amides of Salinomycin and Their C20-oxo Analogues. ChemMedChem, 15(2), 236–246. https://doi.org/10.1002/cmdc.201900593
Czerwonka, Dominika, Alicja Urbaniak, Szymon Sobczak, Sergio Piña-Oviedo, Timothy C. Chambers, Michał Antoszczak, and Adam Huczyński. “Synthesis and Anticancer Activity of Tertiary Amides of Salinomycin and Their C20-oxo Analogues.ChemMedChem 15, no. 2 (January 17, 2020): 236–46. https://doi.org/10.1002/cmdc.201900593.
Czerwonka D, Urbaniak A, Sobczak S, Piña-Oviedo S, Chambers TC, Antoszczak M, et al. Synthesis and Anticancer Activity of Tertiary Amides of Salinomycin and Their C20-oxo Analogues. ChemMedChem. 2020 Jan 17;15(2):236–46.
Czerwonka, Dominika, et al. “Synthesis and Anticancer Activity of Tertiary Amides of Salinomycin and Their C20-oxo Analogues.ChemMedChem, vol. 15, no. 2, Jan. 2020, pp. 236–46. Pubmed, doi:10.1002/cmdc.201900593.
Czerwonka D, Urbaniak A, Sobczak S, Piña-Oviedo S, Chambers TC, Antoszczak M, Huczyński A. Synthesis and Anticancer Activity of Tertiary Amides of Salinomycin and Their C20-oxo Analogues. ChemMedChem. 2020 Jan 17;15(2):236–246.
Journal cover image

Published In

ChemMedChem

DOI

EISSN

1860-7187

Publication Date

January 17, 2020

Volume

15

Issue

2

Start / End Page

236 / 246

Location

Germany

Related Subject Headings

  • Structure-Activity Relationship
  • Pyrans
  • Molecular Conformation
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Drug Screening Assays, Antitumor
  • Dose-Response Relationship, Drug
  • Cells, Cultured
  • Cell Survival
  • Cell Proliferation