RT info:eu-repo/semantics/article
T1 Tuning pH-dependent cytotoxicity in cancer cells by peripheral fluorine substitution on pseudopeptidic cages
A1 Tapia, Lucía
A1 Pérez, Yolanda
A1 Carreira Barral, Israel
A1 Bujons, Jordi
A1 Bolte, Michael
A1 Bedia, Carmen
A1 Solà, Jordi
A1 Quesada Pato, Roberto
A1 Alfonso, Ignacio
K1 Supramolecular chemistry
K1 Cages
K1 Anion binding
K1 Ionophores
K1 Cancer cells
K1 pH
K1 Aqueous-lipid interphase
K1 Ion transport
K1 NMR
K1 Molecular dynamics
K1 Bioquímica
K1 Biochemistry
K1 Química orgánica
K1 Chemistry, Organic
AB 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.
PB Cell Press
SN 2666-3864
YR 2024
FD 2024-09
LK http://hdl.handle.net/10259/9572
UL http://hdl.handle.net/10259/9572
LA eng
NO We are thankful for the funding from the Spanish Research Agency of the Spanish Ministry of Science, Innovation and Universities MICIU/AEI/10.13039/501100011033 (grants  PID2021-128411NB-I00  and  PID2020-117610RB-I00 ) and the European Social Fund.
DS Repositorio Institucional de la Universidad de Burgos
RD 23-nov-2024