Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents

被引：0
作者：
Laura A. Jowett
Ethan N. W. Howe
Vanessa Soto-Cerrato
Wim Van Rossom
Ricardo Pérez-Tomás
Philip A. Gale
机构：
[1] School of Chemistry (F11),Department of Pathology and Experimental Therapeutics
[2] The University of Sydney,undefined
[3] Cancer Cell Biology Research Group,undefined
[4] University of Barcelona,undefined
[5] Chemistry,undefined
[6] University of Southampton,undefined
[7] Highfield,undefined
来源：
Scientific Reports | / 7卷
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摘要：
Prodigiosin is one of the most potent anion transporters in lipid bilayer membranes reported to date. Inspired by the structure of this natural product, we have recently designed and synthesised a new class of H+/Cl− cotransporters named ‘perenosins’. Here we report a new library of indole-based perenosins and their anion transport properties. The new transporters demonstrated superior transmembrane transport efficiency when compared to other indole-based transporters, due to favourable encapsulating effects from the substituents on the perenosin backbone. Anion transport assays were used to determine the mechanism of chloride transport revealing that the compounds function as ‘strict’ HCl cotransporters. Cell viability studies showed that some compounds specifically trigger late-onset cell death after 72 h with a unique correlation to the position of alkyl chains on the perenosins. Further investigations of cell death mechanism showed a mixture of cell cycle arrest and apoptosis was responsible for the observed decrease in cell viability.
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