Effect of modification of betulinic acid at the C3-carbon atom of homolupane triterpenoids on the antiproliferative activity in vitro

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F22%3A00562286" target="_blank" >RIV/61389030:_____/22:00562286 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/22:73616106

Výsledek na webu

<a href="https://doi.org/10.1016/j.jsbmb.2022.106161" target="_blank" >https://doi.org/10.1016/j.jsbmb.2022.106161</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jsbmb.2022.106161" target="_blank" >10.1016/j.jsbmb.2022.106161</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effect of modification of betulinic acid at the C3-carbon atom of homolupane triterpenoids on the antiproliferative activity in vitro

Popis výsledku v původním jazyce

In search of new cytotoxic derivatives based on the lupane scaffold, methyl betulonate and methyl 20,29-dihydrobetulonate were conjugated with Reformatsky reagents to provide homolupanes extended at the C3-carbon atom. Further transformations of the functional groups afforded a series of derivatives with 2-hydroxyethyl and allyl alcohol moieties. Their varying antiproliferative activity in vitro was then investigated in four cancer cell lines and in normal human BJ fibroblasts. In cervical carcinoma HeLa cells, derivatives 5, 6 and 17 were the most promising with lower micromolar IC50s and no toxicity to fibroblasts, thus showing a high therapeutic index. In addition, induction of apoptosis was found in HeLa cells after 24 h treatment with compounds 5, 6, 13 and 29. This newly synthesized series is more interesting than the published lupane and homolupane triterpenes and saponins, due to their nontoxicity towards healthy human cells and stronger cytotoxicity to various cancer cell lines. This approach increases their potential as anticancer agents.

Název v anglickém jazyce

Effect of modification of betulinic acid at the C3-carbon atom of homolupane triterpenoids on the antiproliferative activity in vitro

Popis výsledku anglicky

In search of new cytotoxic derivatives based on the lupane scaffold, methyl betulonate and methyl 20,29-dihydrobetulonate were conjugated with Reformatsky reagents to provide homolupanes extended at the C3-carbon atom. Further transformations of the functional groups afforded a series of derivatives with 2-hydroxyethyl and allyl alcohol moieties. Their varying antiproliferative activity in vitro was then investigated in four cancer cell lines and in normal human BJ fibroblasts. In cervical carcinoma HeLa cells, derivatives 5, 6 and 17 were the most promising with lower micromolar IC50s and no toxicity to fibroblasts, thus showing a high therapeutic index. In addition, induction of apoptosis was found in HeLa cells after 24 h treatment with compounds 5, 6, 13 and 29. This newly synthesized series is more interesting than the published lupane and homolupane triterpenes and saponins, due to their nontoxicity towards healthy human cells and stronger cytotoxicity to various cancer cell lines. This approach increases their potential as anticancer agents.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/GA20-25308S" target="_blank" >GA20-25308S: Modulace cyklin-dependentních kináz pro cílenou léčbu nádorů s molekulárně-definovanou deregulací G1/S fáze buněčného cyklu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

Journal of Steroid Biochemistry and Molecular Biology

ISSN

0960-0760

e-ISSN

—

Svazek periodika

224

Číslo periodika v rámci svazku

NOV

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

106161

Kód UT WoS článku

000840639000001

EID výsledku v databázi Scopus

2-s2.0-85135532005