Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/504f1bce-7f76-422a-9609-bc79428c8ce9
- author
- Borgström, Björn LU ; Huang, Xiaoli LU ; Chygorin, Eduard ; Oredsson, Stina LU and Strand, Daniel LU
- organization
- publishing date
- 2016-04-25
- 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 (ACS)
- external identifiers
-
- scopus:84974589178
- pmid:27326340
- 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
- 2022-04-01 00:45:36
@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}}, keywords = {{Salinomycin; ALDH+; head-to-tail conformation; hydroxamic acid derivate}}, language = {{eng}}, month = {{04}}, number = {{6}}, pages = {{635--640}}, publisher = {{The American Chemical Society (ACS)}}, 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}}, doi = {{10.1021/acsmedchemlett.6b00079}}, volume = {{7}}, year = {{2016}}, }