Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F20%3A00523649" target="_blank" >RIV/61389030:_____/20:00523649 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/20:73604618 RIV/00216275:25310/20:39916447 RIV/00216208:11310/20:10414362

Výsledek na webu

<a href="http://doi.org/10.1016/j.ejmech.2020.112036" target="_blank" >http://doi.org/10.1016/j.ejmech.2020.112036</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>

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 antiproliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI50 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 antiproliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI50 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.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

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

—

Svazek periodika

188

Číslo periodika v rámci svazku

FEB 15

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

13

Strana od-do

112036

Kód UT WoS článku

000515428100039

EID výsledku v databázi Scopus

2-s2.0-85077649747