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

The result's identifiers

  • 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>

Alternative languages

  • 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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10401 - Organic chemistry

Result continuities

  • Project

  • Continuities

    S - Specificky vyzkum na vysokych skolach

Others

  • Publication year

    2021

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    International Journal of Molecular Sciences

  • ISSN

    1661-6596

  • e-ISSN

  • 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

  • UT code for WoS article

    000735654100001

  • EID of the result in the Scopus database