Chloride Transport across Liposomes and Cells by Nontoxic 3-(1H-1,2,3-Triazol-1-yl)benzamides

Abstract

Synthetic anion transmembrane transporters are adding new aspirations for treating channelopathies by replacing defective ion channels. The availability of such suitable candidates is still infrequent due to the associated toxicity. Here, we report 3-(1H-1,2,3-triazol-1-yl)­benzamides as transmembrane anion carriers, nontoxic to cells. The selective and electrogenic chloride transport activity was established by fluorescence and ion selective electrode-based assays. MQAE assay confirmed the chloride uptake into the cells by the nontoxic compounds.

A Benzohydrazide-Based Artificial Ion Channel that Modulates Chloride Ion Concentration in Cancer Cells and Induces Apoptosis by Disruption of Autophagy

“…To understand the mechanism by which compound 1c was mediating cytotoxicity in MDA-MB-231 cells, further studies were performed, which focused on studying the efficacy of compound 1c in transporting Cl – ions into the intracellular matrix. ,,,, The fluorescence of MQAEa cell-permeable Cl – ion-sensitive dyegets quenched in the presence of Cl – ions, thereby indicating intracellular Cl – transport. A time-and-dose-dependent quenching of MQAE fluorescence (λ ex = 350 nm and λ em = 460 nm) was observed (Figure B).…”

Progress and prospects toward supramolecular bioactive ion transporters

“…47 The 3-(1,2,3-triazol-1-yl)benzamide derivatives have recently been developed by our team as a nontoxic transmembrane anion carrier. 48 Very recently, isophthalic acid-based artificial ion channels were also developed by us, which were found to be nontoxic to cells even up to 100 mM concentrations. 49 On the other hand, recent findings have revealed that natural products like prodigiosin, tambjamines, and sphingolipidsderived ionophores are capable of inhibiting the growth of several cancer cells.…”

“…A library of compounds 21a-21e was created to finetune the binding affinity, lipophilicity, and membrane permeability of the system. 48 The dose-responsive ion transport studies using HPTS assay provided the half-maximal activity (EC 50 ) values of 1.68 mM, i.e., 2.5 mol%, relative to lipid concentration for the most active compound 21d and the Hill coefficient ''n'' equal to 1, implying that a single molecule is sufficient to form the active transport complex. Transporter 21d was found to be most selective toward chloride ions, and such selectivity was further confirmed by monitoring its efflux using a chloride ion selective electrode (ISE).…”

Nontoxic Artificial Chloride Channel Formation in Epithelial Cells by Isophthalic Acid‐Based Small Molecules

“…Further, they demonstrated that synthetic anionophores alone or in conjugation with CFTR modulators might represent a potentially useful treatment strategy for CF [13] . Recently, our group reported 3‐(1,2,3‐triazol‐1‐yl)benzamide as a nontoxic transmembrane anion carrier [14] . Herein, we report our newly designed isophthalic acid‐based small molecule channels capable of transporting Cl − ions across cell membranes and exhibiting nontoxic behaviour to cells even at a loading concentration of 100 μM.…”

“…[13] Recently, our group reported 3-(1,2,3-triazol-1-yl)benzamide as a nontoxic transmembrane anion carrier. [14] Herein, we report our newly designed isophthalic acid-based small molecule channels capable of transporting Cl À ions across cell membranes and exhibiting nontoxic behaviour to cells even at a loading concentration of 100 μM.…”