Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity
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, glycosy...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/23/15143 |
| _version_ | 1797462981826576384 |
|---|---|
| author | Jana Rudolfová Vladimír Kryštof Marek Nečas Robert Vícha Michal Rouchal |
| author_facet | Jana Rudolfová Vladimír Kryštof Marek Nečas Robert Vícha Michal Rouchal |
| author_sort | Jana Rudolfová |
| collection | DOAJ |
| description | 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 β-cyclodextrin (β-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 β-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 β-CD, which was probably due to the competitive binding of the corresponding purine nucleoside inside the β-CD cavity. |
| first_indexed | 2024-03-09T17:45:11Z |
| format | Article |
| id | doaj.art-150344cbae4044799a6743d39efc459e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:45:11Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-150344cbae4044799a6743d39efc459e2023-11-24T11:14:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231514310.3390/ijms232315143Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological ActivityJana Rudolfová0Vladimír Kryštof1Marek Nečas2Robert Vícha3Michal Rouchal4Department of Chemistry, Faculty of Technology, Tomas Bata University in Zlín, Vavrečkova 5669, 760 01 Zlín, Czech RepublicDepartment of Experimental Biology, Palacký University, Šlechtitelů 27, 783 71 Olomouc, Czech RepublicDepartment of Chemistry, Faculty of Science, Masaryk University, Kotlářská 2, 602 00 Brno, Czech RepublicDepartment of Chemistry, Faculty of Technology, Tomas Bata University in Zlín, Vavrečkova 5669, 760 01 Zlín, Czech RepublicDepartment of Chemistry, Faculty of Technology, Tomas Bata University in Zlín, Vavrečkova 5669, 760 01 Zlín, Czech RepublicPurine 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 β-cyclodextrin (β-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 β-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 β-CD, which was probably due to the competitive binding of the corresponding purine nucleoside inside the β-CD cavity.https://www.mdpi.com/1422-0067/23/23/15143adamantanepurinenucleosideglycosylationβ-cyclodextrinantiproliferative activity |
| spellingShingle | Jana Rudolfová Vladimír Kryštof Marek Nečas Robert Vícha Michal Rouchal Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity International Journal of Molecular Sciences adamantane purine nucleoside glycosylation β-cyclodextrin antiproliferative activity |
| title | Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity |
| title_full | Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity |
| title_fullStr | Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity |
| title_full_unstemmed | Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity |
| title_short | Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity |
| title_sort | adamantane substituted purine nucleosides synthesis host guest complexes with β cyclodextrin and biological activity |
| topic | adamantane purine nucleoside glycosylation β-cyclodextrin antiproliferative activity |
| url | https://www.mdpi.com/1422-0067/23/23/15143 |
| work_keys_str_mv | AT janarudolfova adamantanesubstitutedpurinenucleosidessynthesishostguestcomplexeswithbcyclodextrinandbiologicalactivity AT vladimirkrystof adamantanesubstitutedpurinenucleosidessynthesishostguestcomplexeswithbcyclodextrinandbiologicalactivity AT mareknecas adamantanesubstitutedpurinenucleosidessynthesishostguestcomplexeswithbcyclodextrinandbiologicalactivity AT robertvicha adamantanesubstitutedpurinenucleosidessynthesishostguestcomplexeswithbcyclodextrinandbiologicalactivity AT michalrouchal adamantanesubstitutedpurinenucleosidessynthesishostguestcomplexeswithbcyclodextrinandbiologicalactivity |