Apoptosis-Inducing Activity of a 2-Hydroxyphenyl Benzamide-Based Self-Assembled Anion Channel

Abstract

Despite the significant interest in designing artificial ion channels, there is limited availability of channel-forming molecules to tackle complex issues, especially in biological systems. Moreover, a major challenge is the scarcity of chloride transporters that can selectively induce toxicity in cancer cells while minimizing harm to normal healthy cells. This work reports a series of 2-hydroxyphenyl benzamide-based small molecules 1 a–1 c, which self-assemble to form barrel rosette-type artificial ion channels that adequately transport chloride ions across membranes. The formation of these ion channels primarily relies on intermolecular hydrogen bonding and π-π stacking interactions, as supported by the analysis of single-crystal X-ray diffraction and molecular dynamics (MD) simulations. Importantly, chloride ion transport by these compounds specifically triggers apoptosis in cancer cells while demonstrating relatively low toxicity toward non-cancerous cell lines.