Cytotoxic anion transporters with light‐regulation properties are highly interesting for the development of anticancer agents with reduced secondary effects. Herein, we present a series of potent diaryl squaramide (SQ) transporters that can be deactivated with light. Liposome‐based assays indicate that the deactivation efficiency depends on the nature of the aryl substituents, with remarkably efficient deactivations observed for cyano‐substituted SQs (i.e., deactivation in only 1 s). Spectroscopic studies suggest that the loss of transport activity is caused by transformation of the SQs into furanone derivatives within the lipid membranes. Finally, cell viability studies show how the cytotoxicity of SQs can be reduced with light, probably by inhibition of an anion transport process in the cell membrane. This study presents the first example of artificial cytotoxic transporters deactivated by direct irradiation in living cells, which can allow selective mitigation of their killing ability.
Galmés et al. (Wed,) studied this question.