Bivalent polyether ionophores: Synthesis and biological evaluation of C2-symmetric salinomycin dimers. Issue 24 (14th June 2017)

• Record Type: Journal Article
• Authors: Antoszczak, Michał; Maj, Ewa; Borgström, Björn; Oredsson, Stina; Huczyński, Adam; Wietrzyk, Joanna; Strand, Daniel
• Is Part Of: Tetrahedron letters. Volume 58:Issue 24(2017)
• Page Start: 2396
• Page End: 2399
• Publication Date: 2017-06-14
• Subjects: Ionophore antibiotics -- Multivalent structures -- Glaser-type coupling reaction -- Anti-proliferative activity -- SRB assay; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2017.05.023
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Two novel classes of C2 -symmetric salinomycin dimers were designed and synthesized. TheC20- dimer was synthesized using a selective bi-directional acylation reaction. The C1 1, 3-diyne dimers were synthesized using a Cu(I)-catalysed Glaser-type coupling. The C20 dimer exhibited activity against cancer cell lines at micromolar concentrations. The C20 dimer showed low toxicity against normal (non-cancer) cells. Abstract: Efficient methods for the synthesis of C2 -symmetric dimers of salinomycin joined at either the C1 or C20 positions are reported. Similarly to the native structure, the C20- O -terephthalate dimer displayed activity in the low μM range against a series of cancer cell lines, while dimers joined at the C1 position were essentially inactive.