Quinine-Based Semisynthetic Ion Transporters with Potential Antiproliferative Activities
Nasim Akhtar, Nirmalya Pradhan, Ganesh Kumar Barik, Soumya Chatterjee, Suvankar Ghosh, Abhishek Saha, Priyadarshi Satpati, Arindam Bhattacharyya, Manas Kumar Santra, Debasis Manna
Abstract
Synthetic ion transporters have attracted tremendous attention for their therapeutic potential against various ion-transport-related diseases, including cancer. Inspired by the structure and biological activities of natural products, we synthesized a small series of squaramide and thiourea derivatives of quinine and investigated their ion transport activities. The involvement of a quinuclidine moiety for the cooperative interactions of Cl– and H+ ions with the thiourea or squaramide moiety resulted in an effectual transport of these ions across membranes. The interference of ionic equilibrium by the potent Cl– ion carrier selectively induced cancer cell death by endorsing caspase-arbitrated apoptosis. In vivo assessment of the potent ionophore showed an efficient reduction in tumor growth with negligible immunotoxicity to other organs.