Phenylhydrazone‐based synthetic receptors are reported as stimuli‐responsive anion transporters. The X‐ray crystallographic studies confirmed the preorganized anion binding E‐state and closed non‐binding Z‐state. The detailed ion transport mechanistic studies confirmed Cl−/anion exchange as the primary ion transport process. Their light‐stimulated E‐to‐Z isomerization led to a substantial decrease in the ion transport activity across the lipid bilayer membrane. Reversible “OFF” and “ON” activity switching was studied by light and acid stimuli, respectively.
Highly substituted
furans are generated by a cascade of formal anti-carbopalladation,
attack of a nucleophilic hydroxy
group, and aromatization by elimination of the emerging dihydrofuran
derivative. Mono-, di-, and trisubstituted furans were obtained in
good to excellent yields. When we attempted to access tetrasubstituted
furan derivatives, an additional rearrangement was observed that resulted
in the formation of chromenes. Follow-up chemistry shows the utility
of TMS as a protecting group for the alkyne moiety.
NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a detoxifying enzyme overexpressed in tumors, plays a key role in protecting cancer cells against oxidative stress and thus has been considered an attractive candidate for activating prodrug(s). Herein, we report the first use of NQO1 for the selective activation of ‘protransporter’ systems in cancer cells leading to the induction of apoptosis. Salicylamides, easily synthesizable small molecules, have been effectively used for efficient H+/Cl− symport across lipid membranes. The ion transport activity of salicylamides was efficiently abated by caging the OH group with NQO1 activatable quinones via either ether or ester linkage. The release of active transporters, following the reduction of quinone caged ‘protransporters’ by NQO1, was verified. Both the transporters and protransporters exhibited significant toxicity towards the MCF‐7 breast cancer line, mediated via the induction of oxidative stress, mitochondrial membrane depolarization, and lysosomal deacidification. Induction of cell death via intrinsic apoptotic pathway was verified by monitoring PARP1 cleavage.
Artificial biomimetic chloride anionophores have shown promising applications as anticancer scaffolds. Importantly, stimuli-responsive chloride transporters that can be selectively activated inside the cancer cells to avoid undesired toxicity to normal,...
Pyrrole-2-carboxamide moiety is well known for its presence in various natural products and its use in anion receptor systems. Here we assess the transmembrane anion transport activity of a series...
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