Synthetic anion transporters for chloride channel replacement and anticancer therapy
A family of small-molecule compounds built on urea, thiourea, and squaramide scaffolds with tunable aryl electron-withdrawing groups. Designed to coordinate anionic guests and facilitate chloride and bicarbonate transport across lipid bilayers, offering potential treatments for cystic fibrosis and other channelopathies, and as anticancer agents that disrupt cellular pH gradients.
Overview
This solution features a family of synthetic small molecules designed to act as artificial anion transporters across biological membranes. The compounds are built on central hydrogen-bond-donor scaffolds such as ureas, thioureas, and squaramides, and are further tuned with a variety of aryl electron-withdrawing substituents to optimize their anion-binding and transport properties.
The primary therapeutic focus is the transmembrane movement of chloride and bicarbonate anions, positioning these molecules as potential replacement therapies for faulty chloride channels associated with cystic fibrosis and other channelopathies. In addition, the compounds have demonstrated potential as anticancer agents by disrupting cellular pH gradients, which can induce apoptosis in targeted cells.
Technical specifications
Core molecular design:
- Central scaffolds featuring multiple hydrogen bond donors (ureas, thioureas, squaramides) for strong anion coordination
- Modulated by aryl electron-withdrawing groups to fine-tune binding affinity, selectivity, and transport activity
- Designed to facilitate chloride and bicarbonate transport across lipid bilayers
Key applications:
- Replacement therapy for defective chloride channels in cystic fibrosis and related channelopathies
- Anticancer therapy through disruption of cellular pH gradients and induction of apoptosis
- Broader potential in any disease context where restoring or modulating anion transport is therapeutically beneficial
Technology readiness level
The compounds have demonstrated proof-of-concept biological activity, including the ability to transport anions across lipid bilayers and to induce apoptosis in cancer cells via pH gradient disruption. Further validation studies are needed to advance toward preclinical development. The technology is at an early-to-mid research stage, suitable for collaborative partnerships aimed at optimization, expanded biological testing, and translational development.
About University of Sydney
The University of Sydney is a comprehensive public research university and one of Australia’s largest, with multi‑campus reach across metropolitan Sydney. Industry partners can access advanced core facilities, testbeds, and prototyping spaces, with labs embedded in or adjacent to hospital precincts at Camperdown–Darlington and Westmead. An industry engagement team and technology transfer office support IP, contracting, licensing, and startup formation, with options to co‑locate teams on campus. Research is supported by competitive national funding, including the Australian Research Council and the National Health and Medical Research Council, plus state and industry partnerships. Proximity to Sydney’s Tech Central innovation precinct and major transport links streamlines collaboration and talent access.
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