Cancer cells use elevated glutathione (GSH) levels as an inner line of defense to evade apoptosis and develop drug resistance.Inthis study,wedescribe anovel 2,4-nitrobenzenesulfonyl (DNS) protected 2-hydroxyisophthalamide system that exploits GSH for its activation into free 2-hydroxyisophthalamide forming supramolecular M + /Cl À channels.Better permeation of the DNS protected compound into MCF-7 cells compared to the free 2-hydroxyisophthalamide and GSHactivatable ion transport resulted in higher cytotoxicity,w hich was associated with increased oxidative stress that further reduced the intracellular GSH levels and altered mitochondrial membrane permeability leading to the induction of the intrinsic apoptosis pathway.T he GSH-activatable transport-mediated cell death was further validated in rat insulinoma cells (INS-1E);w herein the intracellular GSH levels showed ad irect correlation to the resulting cytotoxicity.L astly,t he active compound was found to restrict the growth and proliferation of 3D spheroids of MCF-7 cells with efficiency similar to that of the anticancer drug doxorubicin.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under https://doi.

We report a 2-hydroxy-N1,N3-diarylisophthalamide-based self-assembled channel that cotransports M+/Cl− and induces apoptotic cell death.

Cancer cells use elevated glutathione (GSH) levels as an inner line of defense to evade apoptosis and develop drug resistance. In this study, we describe a novel 2,4‐nitrobenzenesulfonyl (DNS) protected 2‐hydroxyisophthalamide system that exploits GSH for its activation into free 2‐hydroxyisophthalamide forming supramolecular M+/Cl− channels. Better permeation of the DNS protected compound into MCF‐7 cells compared to the free 2‐hydroxyisophthalamide and GSH‐activatable ion transport resulted in higher cytotoxicity, which was associated with increased oxidative stress that further reduced the intracellular GSH levels and altered mitochondrial membrane permeability leading to the induction of the intrinsic apoptosis pathway. The GSH‐activatable transport‐mediated cell death was further validated in rat insulinoma cells (INS‐1E); wherein the intracellular GSH levels showed a direct correlation to the resulting cytotoxicity. Lastly, the active compound was found to restrict the growth and proliferation of 3D spheroids of MCF‐7 cells with efficiency similar to that of the anticancer drug doxorubicin.

Multifunctional organic luminogens exhibiting simultaneous aggregation induced emission (AIE), room-temperature phosphorescence (RTP), and mechanochromism have recently attracted considerable attention owing to their potential applications in optoelectronics and bioimaging. However, a comprehensive correlation among these three distinguished properties is yet to be unveiled, which will help to decipher defined methodologies to design future generation multifunctional organic materials. Herein, we have demonstrated a route to obtain a multifunctional organic luminogen, starting from an ACQphore (TPANDI) by simple structural engineering. We have shown that a slight reduction in length of the planar acceptor moieties can effectively inhibit the undesirable π–π stacking interaction between molecules in the condensed state and thereby cause an ACQ to AIE type transformation from TPANDI to TPANMI and TPAPMI. Both TPANMI and TPAPMI exhibit RTP properties (even in ambient condition) because of the presence of a reasonably low singlet–triplet energy gap (ΔE ST). In our study, these two luminogens were found to be mechano-inactive. Interestingly, an insertion of cyano-ethylene group and benzene linker in between the triphenylamine and phthalimide moieties introduced another luminogen TPACNPMI, which can simultaneously exhibit AIE, RTP, and mechanochromic properties.