Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F20%3A73604618" target="_blank" >RIV/61989592:15310/20:73604618 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/61389030:_____/20:00523649 RIV/00216275:25310/20:39916447 RIV/00216208:11310/20:10414362
Výsledek na webu
<a href="https://www.sciencedirect.com/science/article/pii/S0223523420300039" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523420300039</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2020.112036" target="_blank" >10.1016/j.ejmech.2020.112036</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells
Popis výsledku v původním jazyce
Here, we describe the synthesis and biological characterization of 32 novel phenylalanine and leucine dipeptides modified on both the N and C termini by salicylic acid and aromatic or alicyclic amines, respectively. All compounds displayed anti proliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI(50) values. Treated cells rapidly detached from surface of tissue culture dishes and we found that focal adhesion kinase (FAK), p130CAS and paxillin, which are important regulators of cell adhesion, were dephosphorylated at Y397, Y410 and Y118, respectively. The most potent compound reduced proliferation in the HCT-116 cell line in a dose-dependent manner, as shown by a decrease in 5-bromo-2'-deoxyuridine incorporation into DNA. Furthermore, this compound increased the levels of several apoptotic markers, including activated caspases, and increased site-specific poly-(ADP-ribose)polymerase (PARP) cleavage.
Název v anglickém jazyce
Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells
Popis výsledku anglicky
Here, we describe the synthesis and biological characterization of 32 novel phenylalanine and leucine dipeptides modified on both the N and C termini by salicylic acid and aromatic or alicyclic amines, respectively. All compounds displayed anti proliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI(50) values. Treated cells rapidly detached from surface of tissue culture dishes and we found that focal adhesion kinase (FAK), p130CAS and paxillin, which are important regulators of cell adhesion, were dephosphorylated at Y397, Y410 and Y118, respectively. The most potent compound reduced proliferation in the HCT-116 cell line in a dose-dependent manner, as shown by a decrease in 5-bromo-2'-deoxyuridine incorporation into DNA. Furthermore, this compound increased the levels of several apoptotic markers, including activated caspases, and increased site-specific poly-(ADP-ribose)polymerase (PARP) cleavage.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30107 - Medicinal chemistry
Návaznosti výsledku
Projekt
<a href="/cs/project/GA18-03847S" target="_blank" >GA18-03847S: Pseudopeptidové inhibitory proteasomu</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN
0223-5234
e-ISSN
—
Svazek periodika
188
Číslo periodika v rámci svazku
FEB
Stát vydavatele periodika
FR - Francouzská republika
Počet stran výsledku
13
Strana od-do
"112036-1"-"112036-13"
Kód UT WoS článku
000515428100039
EID výsledku v databázi Scopus
2-s2.0-85077649747