Synthesis and Biological Evaluation of Oxindole Sulfonamide Derivatives as Bruton’s Tyrosine Kinase Inhibitors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F24%3A10158272" target="_blank" >RIV/00098892:_____/24:10158272 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/24:73621988 RIV/61989592:15640/24:73621988

Result on the web

<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202300511" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202300511</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cmdc.202300511" target="_blank" >10.1002/cmdc.202300511</a>

Result language

angličtina

Original language name

Synthesis and Biological Evaluation of Oxindole Sulfonamide Derivatives as Bruton’s Tyrosine Kinase Inhibitors

Original language description

Bruton’s tyrosine kinase (BTK) is a promising molecular target for several human B-cell-related autoimmune disorders, inflammation, and haematological malignancies. The pathogenic alterations in various cancer tissues depend on mutant BTK for cell proliferation and survival, and BTK is also overexpressed in a range of hematopoietic cells. Due to this, BTK is emerging as a potential drug target to treat various human diseases, and several reversible and irreversible inhibitors have been developed and are being developed. As a result, BTK inhibition, clinically validated as an anticancer treatment, is finding great interest in B-cell malignancies and solid tumours. This study focuses on the design and synthesis of new oxindole sulfonamide derivatives as promising inhibitors of BTK with negligible off-target effects. The most cytotoxic compounds with greater basicity were PID-4 (2.29±0.52 μM), PID-6 (9.37±2.47 μM), and PID-19 (2.64±0.88 μM). These compounds caused a selective inhibition of Burkitt’s lymphoma RAMOS cells without significant cytotoxicity in non-BTK cancerous and non-cancerous cell lines. Further, PID-4 showed promising activity in inhibiting BTK and downstream signalling cascades. As a potent inhibitor of Burkitt’s lymphoma cells, PID-4 is a promising lead for developing novel chemotherapeutics.

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

—

OECD FORD branch

30107 - Medicinal 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

ChemMedChem

ISSN

1860-7179

e-ISSN

1860-7187

Volume of the periodical

19

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

15

Pages from-to

"e202300511"

UT code for WoS article

001123464900001

EID of the result in the Scopus database

2-s2.0-85177206044