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Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids

Borgström, Björn LU ; Huang, Xiaoli LU ; Chygorin, Eduard ; Oredsson, Stina LU and Strand, Daniel LU (2016) In ACS Medicinal Chemistry Letters 7(6). p.635-640
Abstract
The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the... (More)
The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH+ cells, a phenotype associated (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Salinomycin, ALDH+, head-to-tail conformation, hydroxamic acid derivate
in
ACS Medicinal Chemistry Letters
volume
7
issue
6
pages
6 pages
publisher
The American Chemical Society
external identifiers
  • scopus:84974589178
  • wos:000377845200019
ISSN
1948-5875
DOI
10.1021/acsmedchemlett.6b00079
language
English
LU publication?
yes
id
504f1bce-7f76-422a-9609-bc79428c8ce9
date added to LUP
2016-06-17 14:58:23
date last changed
2017-03-26 04:43:13
@article{504f1bce-7f76-422a-9609-bc79428c8ce9,
  abstract     = {The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH+ cells, a phenotype associated},
  author       = {Borgström, Björn and Huang, Xiaoli and Chygorin, Eduard  and Oredsson, Stina and Strand, Daniel},
  issn         = {1948-5875},
  keyword      = {Salinomycin,ALDH+,head-to-tail conformation,hydroxamic acid derivate},
  language     = {eng},
  month        = {04},
  number       = {6},
  pages        = {635--640},
  publisher    = {The American Chemical Society},
  series       = {ACS Medicinal Chemistry Letters},
  title        = {Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids},
  url          = {http://dx.doi.org/10.1021/acsmedchemlett.6b00079},
  volume       = {7},
  year         = {2016},
}