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

Small-molecule-based Cl ion carriers are gaining revived attention because of their recently discovered role toward anticancer activity. Herein, we showed that the anticancer agents, PITENINs, have an efficient transmembrane Cl ion transport activity. Theoretical calculations, H NMR titration, and spectrophotometric analysis suggest that the PITENINs strongly bind with a Cl ion. In addition to the lipophilicity, the presence of both acylthiourea and phenolic OH moieties of the compounds plays a crucial role in the transport of Cl ions. Among the tested compounds, and 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 and preferentially promotes apoptotic cell death.