Adamantane-substituted purines and their β-cyclodextrin complexes: Synthesis and biological activity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F70883521%3A28110%2F21%3A63538938" target="_blank" >RIV/70883521:28110/21:63538938 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/22/23/12675" target="_blank" >https://www.mdpi.com/1422-0067/22/23/12675</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms222312675" target="_blank" >10.3390/ijms222312675</a>

Result language

angličtina

Original language name

Adamantane-substituted purines and their β-cyclodextrin complexes: Synthesis and biological activity

Original language description

Cyclin-dependent kinases (CDKs) play an important role in the cell-division cycle. Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. In this study, we proved that the pharmaco-chemical properties of purine-based inhibitors can be improved by appropriate substitution with the adamantane moiety. We prepared ten new purine derivatives with adamantane skeletons that were linked at position 6 using phenylene spacers of variable geometry and polarity. We demonstrated that the adamantane skeleton does not compromise the biological activity, and some of the new purines displayed even higher inhibition activity towards CDK2/cyclin E than the parental compounds. These findings were supported by a docking study, which showed an adamantane scaffold inside the binding pocket participating in the complex stabilisation with non-polar interactions. In addition, we demonstrated that β-cyclodextrin (CD) increases the drug’s solubility in water, although this is at the cost of reducing the biochemical and cellular effect. Most likely, the drug concentration, which is necessary for target engagement, was decreased by competitive drug binding within the complex with β-CD.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

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Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Molecular Sciences

ISSN

1661-6596

e-ISSN

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Volume of the periodical

22

Issue of the periodical within the volume

23

Country of publishing house

CH - SWITZERLAND

Number of pages

20

Pages from-to

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UT code for WoS article

000735654100001

EID of the result in the Scopus database

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