Lupane and 18a-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33160885" target="_blank" >RIV/61989592:15310/16:33160885 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/16:33160885

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0223523416304251" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0223523416304251</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2016.05.029" target="_blank" >10.1016/j.ejmech.2016.05.029</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lupane and 18a-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

Popis výsledku v původním jazyce

Lupane derivatives containing an electronegative substituent in the position 2 of the skeleton are often cytotoxic, however, the most active compounds are not selective enough. To further study the influence of a substituent in the position 2 in lupane and 18a-oleanane derivatives on their biological properties, we prepared a set of 38 triterpenoid compounds, 19 of them new, most of them substituted in the position 2. From betulin, we obtained 2-bromo dihydrobetulonic acid and 2-bromo allobetulon and their substitutions yielded derivatives with various substituents in the position 2 such as amines, amides, thiols, and thioethers. Nitration of allobetulon and dihydrobetulonic acid gave 2-nitro and 2,2-dinitro derivatives. Fifteen derivatives had IC50 < 50 mM on a chemosensitive CCRF-CEM (acute lymphoblastic leukemia) cell line and were tested on another seven cancer cell lines including resistant and two noncancer lines. 2-Amino allobetulin had IC50 4.6 mM and caused significant block of the tumor cells in S and slightly in G2/M transition and caused strong inhibition of DNA and RNA synthesis at 5 IC50. 2-Amino allobetulin is the most active derivative of 18a-oleanane skeletal type prepared in our research group to date.

Název v anglickém jazyce

Lupane and 18a-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

Popis výsledku anglicky

Lupane derivatives containing an electronegative substituent in the position 2 of the skeleton are often cytotoxic, however, the most active compounds are not selective enough. To further study the influence of a substituent in the position 2 in lupane and 18a-oleanane derivatives on their biological properties, we prepared a set of 38 triterpenoid compounds, 19 of them new, most of them substituted in the position 2. From betulin, we obtained 2-bromo dihydrobetulonic acid and 2-bromo allobetulon and their substitutions yielded derivatives with various substituents in the position 2 such as amines, amides, thiols, and thioethers. Nitration of allobetulon and dihydrobetulonic acid gave 2-nitro and 2,2-dinitro derivatives. Fifteen derivatives had IC50 < 50 mM on a chemosensitive CCRF-CEM (acute lymphoblastic leukemia) cell line and were tested on another seven cancer cell lines including resistant and two noncancer lines. 2-Amino allobetulin had IC50 4.6 mM and caused significant block of the tumor cells in S and slightly in G2/M transition and caused strong inhibition of DNA and RNA synthesis at 5 IC50. 2-Amino allobetulin is the most active derivative of 18a-oleanane skeletal type prepared in our research group to date.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CC - Organická chemie

OECD FORD obor

—

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

2016

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

121

Číslo periodika v rámci svazku

OCT

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

12

Strana od-do

120-131

Kód UT WoS článku

000382269700011

EID výsledku v databázi Scopus

—