title: Chloride-Mediated Apoptosis-Inducing Activity of Bis(sulfonamide) Anionophores.
abstract: Transmembrane anion transport modality is enjoying a renewed interest because of recent advances toward anticancer therapy. Here we show bis(sulfonamides) as efficient receptors for selective Cl(-) ion binding and transport across lipid bilayer membranes. Anion-binding studies by (1)H NMR indicate a logical correlation between the acidity of sulfonamide N-H proton and binding strength. Such recognition is influenced further by the lipophilicity of a receptor during the ion-transport process. The anion-binding and transport activity of a bis(sulfonamide) system are far superior compared to those of the corresponding bis(carboxylic amide) derivative. Fluorescent-based assays confirm the Cl(-)/anion antiport as the operational mechanism of the ion transport by bis(sulfonamides). Disruption of ionic homeostasis by the transported Cl(-) ion, via bis(sulfonamide), is found to impose cell death. Induction of a caspase-dependent intrinsic pathway of apoptosis is confirmed by monitoring the changes in mitrochondrial membrane potential, cytochrome c leakage, activation of family of caspases, and nuclear fragmentation studies.
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune , Pune, Maharashtra 411008, India.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Saha
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune , Pune, Maharashtra 411008, India.
authors.forename: Munshi Sahid
authors.initials: MS
authors.lastname: Hossain
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune , Pune, Maharashtra 411008, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Saha
authors.affiliation: Department of Biology, Indian Institute of Science Education and Research Pune , Pune, Maharashtra 411008, India.
authors.forename: Mayurika
authors.initials: M
authors.lastname: Lahiri
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Pune , Pune, Maharashtra 411008, India.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Talukdar
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000838:Anions / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D017136:Ion Transport; D008051:Lipid Bilayers / Q000378:metabolism*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000838:Anions; D002712:Chlorides; D008051:Lipid Bilayers; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D045304:Cytochromes c; D020169:Caspases