Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F17%3A73583919" target="_blank" >RIV/61989592:15110/17:73583919 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389030:_____/17:00482509 RIV/61388963:_____/17:00482509 RIV/61989592:15310/17:73583919

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0223523417307559" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0223523417307559</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2017.09.041" target="_blank" >10.1016/j.ejmech.2017.09.041</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids

Popis výsledku v původním jazyce

To improve the properties of cytotoxic triterpenoid acids 1-5, a large set of hydrophilic esters was synthesized. We choose betulinic acid (1), dihydrobetulinic acid (2), 21-oxoacid 3 along with highly active des-E lupane acids 4 and 5 as a model set of compounds for esterification of which the properties needed to be improved. As ester moieties were used- methoxyethanol and 2-(2-methoxyethoxy)ethanol and glycolic unit (type a-d), pyrrolidinoethanol, piperidinoethanol and morpholinoethanol (type f-h), and monosaccharide groups (type i-I). As a result, 56 triterpenic esters (49 new compounds) were obtained and their cytotoxicity on four cancer cell lines and normal human fibroblasts was tested. All new compounds were fully soluble at all tested concentrations, which used to be a problem of the parent compounds 1 and 2. 16 compounds had IC50 &lt; 10 mu M on at least one cancer cell line, 12 compounds had cytotoxicity of &lt;10 mu M against at least three of four tested cancer cell lines. The highest activity was found for compound 3c (1.8 mu M on MCF7, 2.8 mu M on HeLa, and 1.6 mu M on G-361 cells) which also had no toxicity on non-cancerous BJ fibroblasts at the highest tested concentration (50 mu M). High, selective cytotoxicity was also found in compounds 1k, 2k, 3c, and 3i that are ideal candidates for drug development. Therefore, more studies to identify the mechanism of action were performed in case of 1k, 3c, and 3g such as effects on cell cycle and apoptosis. It was found that compounds 3c and 3g can induce apoptosis via caspase-3 activation and modulation of protein Bc1-2 in G-361 cells. In conclusion, compounds 1k, 3c, and 3g show high and selective cytotoxicity, therefore they are significantly better candidates for anti-cancer drug development than the parent acids 1-5.

Název v anglickém jazyce

Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids

Popis výsledku anglicky

To improve the properties of cytotoxic triterpenoid acids 1-5, a large set of hydrophilic esters was synthesized. We choose betulinic acid (1), dihydrobetulinic acid (2), 21-oxoacid 3 along with highly active des-E lupane acids 4 and 5 as a model set of compounds for esterification of which the properties needed to be improved. As ester moieties were used- methoxyethanol and 2-(2-methoxyethoxy)ethanol and glycolic unit (type a-d), pyrrolidinoethanol, piperidinoethanol and morpholinoethanol (type f-h), and monosaccharide groups (type i-I). As a result, 56 triterpenic esters (49 new compounds) were obtained and their cytotoxicity on four cancer cell lines and normal human fibroblasts was tested. All new compounds were fully soluble at all tested concentrations, which used to be a problem of the parent compounds 1 and 2. 16 compounds had IC50 &lt; 10 mu M on at least one cancer cell line, 12 compounds had cytotoxicity of &lt;10 mu M against at least three of four tested cancer cell lines. The highest activity was found for compound 3c (1.8 mu M on MCF7, 2.8 mu M on HeLa, and 1.6 mu M on G-361 cells) which also had no toxicity on non-cancerous BJ fibroblasts at the highest tested concentration (50 mu M). High, selective cytotoxicity was also found in compounds 1k, 2k, 3c, and 3i that are ideal candidates for drug development. Therefore, more studies to identify the mechanism of action were performed in case of 1k, 3c, and 3g such as effects on cell cycle and apoptosis. It was found that compounds 3c and 3g can induce apoptosis via caspase-3 activation and modulation of protein Bc1-2 in G-361 cells. In conclusion, compounds 1k, 3c, and 3g show high and selective cytotoxicity, therefore they are significantly better candidates for anti-cancer drug development than the parent acids 1-5.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

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

2017

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

140

Číslo periodika v rámci svazku

NOV

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

18

Strana od-do

403-420

Kód UT WoS článku

000414620000030

EID výsledku v databázi Scopus

2-s2.0-85030476976