1H-imidazo[4,5-f][1,10]phenanthroline carbohydrate conjugates: synthesis, DNA interactions and cytotoxic activity
Identifiers
Permanent link (URI): http://hdl.handle.net/10017/51847DOI: https://doi.org/10.1016/j.bioorg.2022.105851
ISSN: 0045-2068
Date
2022-08Bibliographic citation
Bioorganic Chemistry, 2022, v. 125, n. 105851
Keywords
Carbohydrate conjugates
2-aryl-imidazo[4,5-f][1,10]phenanthroline derivatives
G-quadruplex DNA ligands
DNA interactions
Antitumor agents
Project
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)/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
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).
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