One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

ISSN

0223-5234

e-ISSN

1768-3254

Svazek periodika

227

Číslo periodika v rámci svazku

JAN

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

16

Strana od-do

"113952-1"-"113952-16"

Kód UT WoS článku

000713818500032

EID výsledku v databázi Scopus

2-s2.0-85118244266