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oai:gredos.usal.es:10366/1702372026-03-03T01:01:07Zcom_10366_3966com_10366_3947com_10366_3946com_10366_3823col_10366_3967

Temprano, Alvaro G Sanchez de Blas, Beatriz Pérez-Melero, Concepción Espinosa Escudero, Ricardo Antonio Briz Sánchez, Oscar Cinca-Fernando, Paula Llera, Lucia Monte Río, María Jesús Bermejo-Gonzalez, Francisco A García Marín, José Juan Rodríguez Romero, Marta 2026-03-02T09:55:45Z 2026-03-02T09:55:45Z 2024-07-17 Temprano, A. G., Sanchez de Blas, B., Pérez-Melero, C., Espinosa-Escudero, R., Briz, O., Cinca-Fernando, P., ... & Romero, M. R. (2024). Synthesis, Characterization, and Potential Usefulness in Liver Function Assessment of Novel Bile Acid Derivatives with Near-Infrared Fluorescence (NIRBAD). Bioconjugate Chemistry, 35(7), 971-980. 1043-1802 http://hdl.handle.net/10366/170237 10.1021/acs.bioconjchem.4c00168 38958375 1520-4812 [EN]Conventional serum markers often fail to accurately detect cholestasis accompanying many liver diseases. Although elevation in serum bile acid (BA) levels sensitively reflects impaired hepatobiliary function, other factors altering BA pool size and enterohepatic circulation can affect these levels. To develop fluorescent probes for extracorporeal noninvasive hepatobiliary function assessment by real-time monitoring methods, 1,3-dipolar cycloaddition reactions were used to conjugate near-infrared (NIR) fluorochromes with azide-functionalized BA derivatives (BAD). The resulting compounds (NIRBADs) were chromatographically (FC and PTLC) purified (>95%) and characterized by fluorimetry, 1H NMR, and HRMS using ESI ionization coupled to quadrupole TOF mass analysis. Transport studies using CHO cells stably expressing the BA carrier NTCP were performed by flow cytometry. Extracorporeal fluorescence was detected in anesthetized rats by high-resolution imaging analysis. Three NIRBADs were synthesized by conjugating alkynocyanine 718 with cholic acid (CA) at the COOH group via an ester (NIRBAD-1) or amide (NIRBAD-3) spacer, or at the 3α-position by a triazole link (NIRBAD-2). NIRBADs were efficiently taken up by cells expressing NTCP, which was inhibited by taurocholic acid (TCA). Following i.v. administration of NIRBAD-3 to rats, liver uptake and consequent release of NIR fluorescence could be extracorporeally monitored. This transient organ-specific handling contrasted with the absence of release to the intestine of alkynocyanine 718 and the lack of hepatotropism observed with other probes, such as indocyanine green. NIRBAD-3 administration did not alter serum biomarkers of hepatic and renal toxicity. NIRBADs can serve as probes to evaluate hepatobiliary function by noninvasive extracorporeal methods. This study has been funded by the Spanish Ministry of Science and Innovation (Proyectos de Generación de Conocimiento 2022: PID2022-140210OB-I00); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain, cofunded by the European Regional Development Fund/European Social Fund, “Investing in your future” (PI19/00819, PI20/00189, PI22/00526, and PI23/00681); CIBERehd (EHD15PI05/2016); “Junta de Castilla y Leon” (SA074P20, SA113P23, and GRS 2322/A/21); AECC Scientific Foundation (2023/2027), Spain; Fundació Marato TV3, Spain (201916-31); “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER 0348-CIE-6-E), Spain; and FEEH, Juan Cordoba Fellowship, Grant 2021, University of Salamanca (“Fundación General: Plan TCUE 2015–2017″, Plan TCUE (ITR) 2018–2020 (2021) and “Programa de financiación de grupos de investigación. Modalidad C2, 2019–2020”). eng ACS Publications Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Novel near infrared Bile Acid Novel near-infrared bile acid derivatives NIRBAD Liver function Liver Liver Function Tests Rats Bile Acids and Salts Animals Fluorescent Dyes Fluorescence CHO Cells 2411 Fisiología Humana 2411.07 Fisiología de la Digestión 2302.18 Lípidos 2403 Bioquímica 2301.10 Espectroscopia de Masas 2209.09 Radiación Infrarroja 2301.08 Espectroscopia de Infrarrojos 2301.09 Espectroscopia de Resonancia Magnética células CHO animales fluorescencia colorantes fluorescentes ratas ácidos y sales biliares pruebas de función hepática hígado Synthesis, Characterization, and Potential Usefulness in Liver Function Assessment of Novel Bile Acid Derivatives with Near-Infrared Fluorescence (NIRBAD). info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://pubs.acs.org/doi/10.1021/acs.bioconjchem.4c00168 PID2022-140210OB-I00 PI19/00819 PI20/00189 PI22/00526 PI23/00681 EHD15PI05/2016 SA074P20 SA113P23 GRS 2322/A/21 Bioconjugate Chemistry 35 7 971 980