Development of pyrimidine-cinnamamide hybrids as potential anticancer agents: A rational design approach

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73616090" target="_blank" >RIV/61989592:15310/22:73616090 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0022286022012509" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0022286022012509</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molstruc.2022.133594" target="_blank" >10.1016/j.molstruc.2022.133594</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Development of pyrimidine-cinnamamide hybrids as potential anticancer agents: A rational design approach

Popis výsledku v původním jazyce

Pyrimidine is a privileged scaffold and part of many anti-cancer drugs, whereas cinnamamides are present in many natural products. The present work reports the rational design and synthesis of 26 novel pyrimidine and cinnamamide hybrid analogs with further optimization in the core structure. The synthesized derivatives were tested against K-562 (chronic myeloid leukemia), MV4-11 (acute myeloid leukemia), G361 (malignant melanoma), and HCC827 (lung adenocarcinoma) cell lines. Compounds 10j, 10m, 10r, and 10t displayed low micromolar potency against leukemia cell lines. 10m and 10r were the most potent analogs against G361 and HCC827 cell lines. Subsequently, structure-activity relationship study was carried out and revealed the nitro substitution was unfavorable for the activity. Cellular effects of compounds 10j and 10t were studied in the most sensitive cell line K562. The compounds arrested the cell cycle in G2/M phases and induced caspase-independent cell death.

Název v anglickém jazyce

Development of pyrimidine-cinnamamide hybrids as potential anticancer agents: A rational design approach

Popis výsledku anglicky

Pyrimidine is a privileged scaffold and part of many anti-cancer drugs, whereas cinnamamides are present in many natural products. The present work reports the rational design and synthesis of 26 novel pyrimidine and cinnamamide hybrid analogs with further optimization in the core structure. The synthesized derivatives were tested against K-562 (chronic myeloid leukemia), MV4-11 (acute myeloid leukemia), G361 (malignant melanoma), and HCC827 (lung adenocarcinoma) cell lines. Compounds 10j, 10m, 10r, and 10t displayed low micromolar potency against leukemia cell lines. 10m and 10r were the most potent analogs against G361 and HCC827 cell lines. Subsequently, structure-activity relationship study was carried out and revealed the nitro substitution was unfavorable for the activity. Cellular effects of compounds 10j and 10t were studied in the most sensitive cell line K562. The compounds arrested the cell cycle in G2/M phases and induced caspase-independent cell death.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical 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

JOURNAL OF MOLECULAR STRUCTURE

ISSN

0022-2860

e-ISSN

1872-8014

Svazek periodika

1267

Číslo periodika v rámci svazku

NOV

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

"133594-1"-"133594-12"

Kód UT WoS článku

000855988900010

EID výsledku v databázi Scopus

2-s2.0-85133293150