Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30105 - Physiology (including cytology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

—

Volume of the periodical

140

Issue of the periodical within the volume

NOV

Country of publishing house

FR - FRANCE

Number of pages

18

Pages from-to

403-420

UT code for WoS article

000414620000030

EID of the result in the Scopus database

2-s2.0-85030476976