Synthesis and biological evaluation of triterpenoid thiazoles derived from betulonic acid, dihydrobetulonic acid, and ursonic acid

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F20%3A73603809" target="_blank" >RIV/61989592:15110/20:73603809 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/20:73603809

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0223523419309584" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523419309584</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2019.111806" target="_blank" >10.1016/j.ejmech.2019.111806</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and biological evaluation of triterpenoid thiazoles derived from betulonic acid, dihydrobetulonic acid, and ursonic acid

Popis výsledku v původním jazyce

In this work, 35 new derivatives of betulonic, dihydrobetulonic and ursonic acid were prepared including 30 aminothiazoles and all of them were tested for their in vitro cytotoxic activity in eight cancer cell lines and two non-cancer fibroblasts. Compounds with the IC50 below 5 mu M in CCRF-CEM cells and low toxicity in non-cancer fibroblasts (4m, Sc, 5m, 6c, 6m, 7b, and 7c) were further subjected to tests of pharmacological parameters yielding the final set for advanced biological evaluation (4m, 5m, 6m, and 7b). It was proved by several methods, that all of them trigger apoptosis via the intrinsic pathway and derivatives 5m and 7b are the most effective (IC50 2.4 mu M and 3.6 They are the best candidates to become potentially new anticancer drugs and will be subjected to in vivo tests in mice. In addition, compounds 6b and 6c deserve more attention because their activity is not limited only to chemosensitive CCRF-CEM cell line. Specifically, compound 6b is highly active against K562 leukemic cell line (0.7 mu M) and its IC50 activity in colon cancer HCT116 cell line is 1.0 mu M. Compound 6c is active in both normal K562 and resistant K562-TAX cell lines (IC50 3.4 mu M and 5.4 mu M) and both colon cancer cell lines (HCT116 and HCT116p53(-/-) , IC(50)3.5 mu M and 3.4 mu M).

Název v anglickém jazyce

Synthesis and biological evaluation of triterpenoid thiazoles derived from betulonic acid, dihydrobetulonic acid, and ursonic acid

Popis výsledku anglicky

In this work, 35 new derivatives of betulonic, dihydrobetulonic and ursonic acid were prepared including 30 aminothiazoles and all of them were tested for their in vitro cytotoxic activity in eight cancer cell lines and two non-cancer fibroblasts. Compounds with the IC50 below 5 mu M in CCRF-CEM cells and low toxicity in non-cancer fibroblasts (4m, Sc, 5m, 6c, 6m, 7b, and 7c) were further subjected to tests of pharmacological parameters yielding the final set for advanced biological evaluation (4m, 5m, 6m, and 7b). It was proved by several methods, that all of them trigger apoptosis via the intrinsic pathway and derivatives 5m and 7b are the most effective (IC50 2.4 mu M and 3.6 They are the best candidates to become potentially new anticancer drugs and will be subjected to in vivo tests in mice. In addition, compounds 6b and 6c deserve more attention because their activity is not limited only to chemosensitive CCRF-CEM cell line. Specifically, compound 6b is highly active against K562 leukemic cell line (0.7 mu M) and its IC50 activity in colon cancer HCT116 cell line is 1.0 mu M. Compound 6c is active in both normal K562 and resistant K562-TAX cell lines (IC50 3.4 mu M and 5.4 mu M) and both colon cancer cell lines (HCT116 and HCT116p53(-/-) , IC(50)3.5 mu M and 3.4 mu M).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic 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

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

185

Číslo periodika v rámci svazku

JAN

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

18

Strana od-do

"111806-1"-"111806-18"

Kód UT WoS článku

000503099900027

EID výsledku v databázi Scopus

2-s2.0-85074176113