Small Molecule-Based Highly Active and Selective K+ Transporters with Potent Anticancer Activities.
Nano Lett
; 21(3): 1384-1391, 2021 02 10.
Article
em En
| MEDLINE
| ID: mdl-33464086
ABSTRACT
We report here a novel class of cation transporters with extreme simplicity, opening a whole new dimension of scientific research for finding small molecule-based cation transporters for therapeutic applications. Comprising three modular components (a headgroup, a flexible alkyl chain-derived body, and a crown ether-derived foot for ion binding), these transporters efficiently (EC50 = 0.18-0.41 mol % relative to lipid) and selectively (K+/Na+ selectivity = 7.0-9.5) move K+ ions across the membrane. Importantly, the most active (EC50 = 0.18-0.22 mol %) and highly selective series of transporters A12, B12, and C12 concurrently possess potent anticancer activities with IC50 values as low as 4.35 ± 0.91 and 6.00 ± 0.13 µM toward HeLa and PC3 cells, respectively. Notably, a mere replacement of the 18-crown-6 unit in the structure with 12-crown-4 or 15-crown-5 units completely annihilates the cation-transporting ability.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Canais de Potássio
Idioma:
En
Revista:
Nano Lett
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China