Ferrocene- and ruthenium arene-containing glycomimetics as selective inhibitors of human galectin-1 and -3

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985858%3A_____%2F24%3A00599696" target="_blank" >RIV/67985858:_____/24:00599696 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/24:00599696 RIV/61388963:_____/24:00599696 RIV/00216224:14310/24:00137750 RIV/00209805:_____/24:00080118 and 2 more

Result on the web

<a href="https://pubs.rsc.org/en/content/articlepdf/2024/qi/d4qi01555j" target="_blank" >https://pubs.rsc.org/en/content/articlepdf/2024/qi/d4qi01555j</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/D4QI01555J" target="_blank" >10.1039/D4QI01555J</a>

Result language

angličtina

Original language name

Ferrocene- and ruthenium arene-containing glycomimetics as selective inhibitors of human galectin-1 and -3

Original language description

Galectins are a family of β-galactoside-binding proteins with an evolutionarily conserved carbohydrate recognition domain. Their dysregulation has been implicated in physiological and pathological processes, including fibrotic disorders, inflammation, and cancer. For example, elevated levels of galectin-1 contribute to tumor cell migration and immune evasion, whereas overexpression of galectin-3 is associated with increased invasiveness and the formation of metastasis. Pharmacological inhibition of these galectins is a promising therapeutic strategy to counteract their oncogenic effects. In this study, we synthesized a novel series of galectin inhibitors with ferrocene and ruthenium arene motifs attached to lactose, N-acetyllactosamine, or thiodigalactoside scaffolds. We determined their binding affinity toward human galectin-1 (hgal-1) and the CRD domain of human galectin-3 (hgal-3-CRD) using fluorescence polarization, intrinsic fluorescence of galectin tryptophan residues, and isothermal titration calorimetry. The ferrocene analogs exhibited superior affinity for both hgal-1 and hgal-3-CRD compared with ruthenium arenes. In particular, a symmetrical diferrocene thiodigalactoside complex exhibited low nanomolar affinity for hgal-1 and selectivity over hgal-3-CRD. Asymmetrical monoferrocene thiodigalactoside complexes exhibited nanomolar affinity and good selectivity for hgal-3-CRD. Chronopotentiometric stripping analysis demonstrated that the inhibitors stabilized hgal-1 against destabilization by electric field effects.19F{ 1H} NMR experiments and molecular dynamics simulations suggested that the incorporation of thenferrocene motif limited the accessible binding modes to hgal-3-CRD whereas binding to hgal-1 remained unrestricted, resulting in attenuated binding affinities to hgal-3-CRD and selectivity for hgal-1. These results open new possibilities for the design and optimization of therapeutic organometallic galectin inhibitors.

Czech name

—

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

—

OECD FORD branch

10402 - Inorganic and nuclear chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Inorganic Chemistry Frontiers

ISSN

2052-1553

e-ISSN

2052-1553

Volume of the periodical

11

Issue of the periodical within the volume

21

Country of publishing house

GB - UNITED KINGDOM

Number of pages

22

Pages from-to

7588-7609

UT code for WoS article

001319761900001

EID of the result in the Scopus database

2-s2.0-85205443201