1H-imidazo[4,5-f][1,10]phenanthroline carbohydrate conjugates: synthesis, DNA interactions and cytotoxic activity
Identificadores
Enlace permanente (URI): http://hdl.handle.net/10017/51847DOI: https://doi.org/10.1016/j.bioorg.2022.105851
ISSN: 0045-2068
Fecha de publicación
2022-08Cita bibliográfica
Bioorganic Chemistry, 2022, v. 125, n. 105851
Palabras clave
Carbohydrate conjugates
2-aryl-imidazo[4,5-f][1,10]phenanthroline derivatives
G-quadruplex DNA ligands
DNA interactions
Antitumor agents
Proyectos
MICINN y MINECO(PID2019-108251RB-I00/AEI/10.13039/501100011033), CAM (YEI,PEJ-2017-AI/SAL-6160, P.G.) y UAH
(CCG2016/EXP-044, CCG2018/EXP-024, CCG2020/CC-024y UAH-AE-2017-2).
info:eu-repo/grantAgreement/MINECO//CTQ2015-72625-EXP/ES/EXPLORANDO EL DESARROLLO DE BIS-OLIGONUCLEOTIDOS \"GRAPA\" PARA EL ANCLAJE COVALENTE DE COMPONENTES CELULARES IN VIVO. UN NUEVO HORIZONTE EN TERAPIAS ANTI-CANCER/
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-108251RB-I00/ES/SISTEMAS METALO-ORGANICOS MULTIFUNCIONALES BASADOS EN CONJUGADOS DE CARBOHIDRATOS, LIPIDOS O ACIDOS NUCLEICOS. RECONOCIMIENTO DE G4 Y ACTIVIDAD ANTITUMORAL (MMOC-G4)/
Tipo de documento
info:eu-repo/semantics/article
Versión
info:eu-repo/semantics/publishedVersion
Derechos
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Derechos de acceso
info:eu-repo/semantics/openAccess
Resumen
Here we present a novel family of carbohydrate conjugates based on the 2-aryl-imidazo[4,5-f][1,10]phenanthroline core modified with carbohydrates (carb-APIPs). The hybrid compounds were prepared by direct treatment of the unprotected carbohydrate with 2-(4-aminophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (APIP). The N-glycosylation reactions with the monosaccharides tested afforded stereoselectively the more stable N-beta-glycopyranosylamines that, in solution, underwent a dynamic equilibrium leading to anomeric mixtures with a small participation of the alfa isomer. DNA interaction experiments with telomeric G-quadruplex DNA included DNA FRET melting assays, circular dichroism, and equilibrium dialysis and revealed that the novel carb-APIPs bind the G-quadruplex structure with high affinity. Interestingly, the presence of the carbohydrate confers good selectivity towards the telomeric quadruplex structure, as suggested by competition DNA FRET melting assays. Besides the extended aromatic surface that allows pi-stacking interactions, the carbohydrate part of the conjugate may contribute to groove binding recognition, as indicated by viscosity experiments. In addition, the novel carb-APIPs showed significant cytotoxic properties in PC3 and HeLa cells and, to a lesser extent, in MCF7 cells and normal human fibroblasts (HFF1).
Ficheros en el ítem
Ficheros | Tamaño | Formato |
|
---|---|---|---|
Gratal_1H-imidazo_BioorgChem_2 ... | 2.541Mb |
|
Ficheros | Tamaño | Formato |
|
---|---|---|---|
Gratal_1H-imidazo_BioorgChem_2 ... | 2.541Mb |
|
Colecciones
- QUIMORG - Artículos [128]