2026-04-19T12:21:53Zhttps://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 e5c671d5-cd02-4202-9594-268754218f2a 600 Pérez, Yolanda ad4c62f5-252c-444e-8680-16d10aa21308 600 Carreira Barral, Israel 763 600 0000-0002-4835-8752 Bujons, Jordi d31efc34-cc1e-4416-8542-fc4c7e90f849 Bolte, Michael ce4f3a32-93f0-463d-bed3-b63109a37a12 600 Bedia, Carmen 7087f803-39f1-42c1-8aa0-0ab561121479 Solà, Jordi a9ce56cc-0392-4b7f-8612-46d7197559d0 600 Quesada Pato, Roberto 458 600 0000-0003-2764-7157 Alfonso, Ignacio 6f8da303-9423-4b68-9938-8aa263489bb6 600 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. 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. application/pdf application/zip video/mp4 eng Cell Press Cell Reports Physical Science. 2024, V. 5, n. 9, 102152 https://doi.org/10.1016/j.xcrp.2024.102152 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PID2021-128411NB-I00/ES/SISTEMAS QUIMICOS COMPLEJOS DINAMICOS: APLICACIONES EN ORGANOCATALISIS Y RECONOCIMIENTO BIOMOLECULAR/ info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica, Técnica y de Innovación 2017-2020/PID2020-117610RB-I00/ES/SMALL MOLECULE TRANSMEMBRANE ANION CARRIERS FOR BIOLOGICAL APPLICATIONS/ Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Supramolecular chemistry Cages Anion binding Ionophores Cancer cells pH Aqueous-lipid interphase Ion transport NMR Molecular dynamics Bioquímica Química orgánica Biochemistry Chemistry, Organic Tuning pH-dependent cytotoxicity in cancer cells by peripheral fluorine substitution on pseudopeptidic cages info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Cell Reports Physical Science 5 9 102152 THUMBNAIL Tapia-crps_2024.pdf.jpg Tapia-crps_2024.pdf.jpg IM Thumbnail image/jpeg 3421 https://riubu.ubu.es/bitstream/10259/9572/4/Tapia-crps_2024.pdf.jpg 357a1eba441370cfbbcb63eec3370f84 MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/9572/3/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/9572/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Tapia-crps_2024.pdf Tapia-crps_2024.pdf application/pdf 5815718 https://riubu.ubu.es/bitstream/10259/9572/1/Tapia-crps_2024.pdf cb0fd902f50d94786f1a16cd8721ca28 MD5 1 Tapia-crps_2024-Supplemental_information.zip Tapia-crps_2024-Supplemental_information.zip Información suplementaria application/zip 137747042 https://riubu.ubu.es/bitstream/10259/9572/5/Tapia-crps_2024-Supplemental_information.zip 41d5ac7febe86035724295b485819757 MD5 5 10259/9572 oai:riubu.ubu.es:10259/9572 2024-09-27 12:00:17.565 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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