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Chemistry cl lynch5/30/2023 ![]() ![]() Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death. Ion transporters, therefore, represent an attractive approach for regulating cellular processes that are normally controlled tightly by homeostasis. However, they do not activate the caspase-independent apoptotic pathway associated with the apoptosis-inducing factor. ![]() Cell experiments show that the ion transporters induce the sodium chloride influx, which leads to an increased concentration of reactive oxygen species, release of cytochrome c from the mitochondria and apoptosis via caspase activation. Removing either ion from the extracellular media or blocking natural sodium channels with amiloride prevents this effect. Here we show that two pyridine diamide-strapped calixpyrroles induce coupled chloride anion and sodium cation transport in both liposomal models and cells, and promote cell death by increasing intracellular chloride and sodium ion concentrations. However, a direct correlation between a change in cellular chloride anion concentration and cytotoxicity has not been established for synthetic ion carriers. Anion transporters based on small molecules have received attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis. ![]()
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