Synthesis and Pharmacological Effects of Diosgenin-Betulinic Acid Conjugates

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F20%3A43920394" target="_blank" >RIV/60461373:22330/20:43920394 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389030:_____/20:00531907 RIV/61388963:_____/20:00531907 RIV/68407700:21340/20:00342222 RIV/61989592:15310/20:73604744

Výsledek na webu

<a href="https://www.mdpi.com/1420-3049/25/15/3546/htm" target="_blank" >https://www.mdpi.com/1420-3049/25/15/3546/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules25153546" target="_blank" >10.3390/molecules25153546</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and Pharmacological Effects of Diosgenin-Betulinic Acid Conjugates

Popis výsledku v původním jazyce

The target diosgenin-betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate7showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50= 6.5 +/- 1.1 mu M), in contrast to the conjugate8showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition,5showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates3and4showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.

Název v anglickém jazyce

Synthesis and Pharmacological Effects of Diosgenin-Betulinic Acid Conjugates

Popis výsledku anglicky

The target diosgenin-betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate7showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50= 6.5 +/- 1.1 mu M), in contrast to the conjugate8showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition,5showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates3and4showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.

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

Molecules

ISSN

1420-3049

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

—

Kód UT WoS článku

000559001100001

EID výsledku v databázi Scopus

2-s2.0-85089171176