Towards “drug-like” indole-based transmembrane anion transporters

Chloride, carboxylate and carbonate transport by ortho-phenylenediamine-based bisureas

“…15,44 In contrast, the nitrophenyl group is a known toxicophore. 58 The disruption of intracellular pH (pH i ) has been suggested as a strategy for cancer treatment.…”

“…14 By considering these guidelines we generated transporters that exhibit biological activity in vivo, such as uorinated molecules based on indolylurea/thiourea 15 scaffolds that show promise as anticancer agents. By synthesising transporters that obey the rules of thumb dened by Lipinski and others, the possibility that these compounds will be biologically compatible is greater, i.e.…”

“…62 Molecules capable of facilitating HCl symport and Cl À /HCO 3 À antiport have been shown to induce apoptosis by facilitating ion transport processes that lower pH i . 15,44,63 All of the compounds that facilitated a reduction in pH i function as Cl À /NO 3 À and Cl À /HCO 3 À antiport agents in vesicle based assays. In addition, the most active transporter (compound 6) has been shown to facilitate HCl co-transport.…”

Anion Receptors Based on Organic Frameworks: Recent Advances

“…The next step in the development of synthetic transmembrane anion transporters is to study transport processes in cells and the effects of transport on cell viability. This work has begun recently with the effects of anion transporters on a range of cancer cell lines studied upon addition of tren-based tris-ureas and tris-thioureas [24], indole-functionalised ureas and thioureas [16] and tambjamines [25] with all these systems depolarising acidic compartments within the cells and triggering apoptosis. Recently Gale, Sessler, Shin and co-workers have shown that pyridinedicarboxamide strapped calixpyrroles 40 and 41 can mediate the transport of chloride in Fischer rat thyroid (FRT) cells that express yellow fluorescent protein (the protein fluorescence is partially quenched upon influx of chloride into the cells).…”

“…Up until this point, most studies had focused on chloride transport; however, since then studies have expanded to other anions including bicarbonate [14,15], the transport of which, like chloride, is impaired through the cystic fibrosis transmembrane regulator protein in the epithelial cell membranes of cystic fibrosis patients. There has also been a move from more complex supramolecular transporters to simpler more "drug-like" molecules [16]. For example, in 2013 Gale and co-workers conducted a quantitative structure-activity relationship (QSAR) study using P.A.…”