Chloride Ion Transport by PITENINs across the Phospholipid Bilayers of Vesicles and Cells

Small molecule-based Cl─ ion carriers are relishing a revived attention because of their recently discovered role towards the anticancer activity. Herein, we showed that the anticancer agents, PITENINs, have an efficient transmembrane Cl─ ion transport activity. Theoretical calculations, 1H NMR titration, and spectrophotometric analysis suggest that the PITENINs strongly bind with the Cl─ ion. In addition to the lipophilicity, the presence of both acylthiourea, and phenolic OH moieties of the compounds play a crucial role in the transport of Cl─ ion. Among the tested compounds, PIT-1 and DM-PIT-1 showed higher Cl─ ion selectivity and transport efficiency. Mechanistic studies demonstrated that the potent compounds, follow the H+/Cl─ transport pathway. Cellular activity studies showed that the disruption of Cl─ ion homeostasis by PIT-1 and DM-PIT-1 preferentially promotes apoptotic cell death.