2026-06-29T21:08:05Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/95722024-09-27T10:00:17Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925

Tapia, Lucía Pérez, Yolanda Carreira Barral, Israel Bujons, Jordi Bolte, Michael Bedia, Carmen Solà, Jordi Quesada Pato, Roberto Alfonso, Ignacio 2024-09-26T12:19:43Z 2024-09-26T12:19:43Z 2024-09 2666-3864 http://hdl.handle.net/10259/9572 10.1016/j.xcrp.2024.102152 The acidic microenvironment of solid tumors is a potential source of selectivity in the anti-cancer activity of ionophores, which requires delicate control of their biophysical properties. In this context, we have systematically studied fluorine substitutions in the aromatic side chains of HCl-binding pseudopeptidic cages. Interconnected factors like chloride binding, protonation, lipophilicity, and conformation and diffusiveness of the cages can impact their ability to transport HCl through the aqueous-lipid interphase, as demonstrated by robust experimental (X-ray, nuclear magnetic resonance [NMR], fluorescence) and theoretical results. The fine-tuning of these properties allows the modulation of their pH-dependent cytotoxicity against cancer cells, from essentially non-cytotoxic at pH 7.5 (like the extracellular surroundings of healthy tissues) to highly toxic in slightly acidic microenvironments (like those around solid tumors). Thus, a distal fluorine substitution produces a big impact on the physicochemical and biological properties of the cages, improving their selectivity as potential therapeutic ionophores. eng http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Atribución 4.0 Internacional Supramolecular chemistry Cages Anion binding Ionophores Cancer cells pH Aqueous-lipid interphase Ion transport NMR Molecular dynamics Tuning pH-dependent cytotoxicity in cancer cells by peripheral fluorine substitution on pseudopeptidic cages info:eu-repo/semantics/article