Adamantane-Substituted Purine Nucleosides: Synthesis, Host-Guest Complexes with β-Cyclodextrin and Biological Activity

Autor: Jana Rudolfová, Vladimír Kryštof, Marek Nečas, Robert Vícha, Michal Rouchal
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 23; Issue 23; Pages: 15143
ISSN: 1422-0067
Popis: Purine nucleosides represent an interesting group of nitrogen heterocycles, showing a wide range of biological effects. In this study, we designed and synthesized a series of 6,9-disubstituted and 2,6,9-trisubstituted purine ribonucleosides via consecutive nucleophilic aromatic substitution, glycosylation, and deprotection of the ribofuranose unit. We prepared eight new purine nucleosides bearing unique adamantylated aromatic amines at position 6. Additionally, the ability of the synthesized purine nucleosides to form stable host-guest complexes with beta-cyclodextrin (beta-CD) was confirmed using nuclear magnetic resonance (NMR) and mass spectrometry (ESI-MS) experiments. The in vitro antiproliferative activity of purine nucleosides and their equimolar mixtures with beta-CD was tested against two types of human tumor cell line. Six adamantane-based purine nucleosides showed an antiproliferative activity in the micromolar range. Moreover, their effect was only slightly suppressed by the presence of beta-CD, which was probably due to the competitive binding of the corresponding purine nucleoside inside the beta-CD cavity.
/0.0/0.0/18_046/0015974, CZ.02.1.01; IGA/FT/2019/007, IGA/FT2018/001; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: LM2018127; Grantová Agentura České Republiky, GA ČR: 21-06553S
Internal Founding Agency of Tomas Bata University in Zlin [IGA/FT2018/001, IGA/FT/2019/007]; Czech Science Foundation [21-06553S]; MEYS CR [LM2018127]; European Regional Development Fund-Project "UP CIISB" [CZ.02.1.01./0.0/0.0/18_046/0015974]
Databáze: OpenAIRE
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