One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73616085" target="_blank" >RIV/61989592:15310/22:73616085 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0223523421008011" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523421008011</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2021.113952" target="_blank" >10.1016/j.ejmech.2021.113952</a>
Alternative languages
Result language
angličtina
Original language name
One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents
Original language description
In the current study, we report on the development of novel series of pyrazolo[3,4-b]pyridine derivatives (8a-u, 11a-n, and 14a,b) as potential anticancer agents. The prepared pyrazolo[3,4-b]pyridines have been screened for their antitumor activity in vitro at NCI-DTP. Thereafter, compound 8a was qualified by NCI for full panel five-dose assay to assess its GI(50), TGI and LC50 values. Compound 8a showed broadspectrum anti-proliferative activities over the whole NCI panel, with outstanding growth inhibition full panel GI(50) (MG-MID) value equals 2.16 mu M and subpanel GI(50) (MG-MID) range: 1.92-2.86 mu M. Furthermore, pyrazolo[3,4-b]pyridines 8a, 8e-h, 8o, 8u, 11a, 11e, 11h, 11l and 14a-b were assayed for their antiproliferative effect against a panel of leukemia cell lines (K562, MV4-11, CEM, RS4;11, ML-2 and KOPN-8) where they possessed moderate to excellent anti-leukemic activity. Moreover, pyrazolo[3,4-b] pyridines 8o, 8u, 14a and 14b were further explored for their effect on cell cycle on RS4;11 cells, in which they dose-dependently increased populations of cells in G2/M phases. Finally we analyzed the changes of selected proteins (HOXA9, MEIS1, PARP, BcL-2 and McL-1) related to cell death and viability in RS4;11 cells via Western blotting. Collectively, the obtained results suggested pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b as promising lead molecules for further optimization to develop more potent and efficient anticancer candidates.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN
0223-5234
e-ISSN
1768-3254
Volume of the periodical
227
Issue of the periodical within the volume
JAN
Country of publishing house
FR - FRANCE
Number of pages
16
Pages from-to
"113952-1"-"113952-16"
UT code for WoS article
000713818500032
EID of the result in the Scopus database
2-s2.0-85118244266