Synthesis and evaluation of Na⁺/K⁺-ATP-ase inhibiting and cytotoxic in vitro activities of oleandrigenin and its selected 17β-(butenolidyl)- and 17β-(3-furyl)- analogues

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F20%3A00532720" target="_blank" >RIV/61389030:_____/20:00532720 - isvavai.cz</a>

Výsledek na webu

<a href="http://doi.org/10.1016/j.ejmech.2020.112520" target="_blank" >http://doi.org/10.1016/j.ejmech.2020.112520</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2020.112520" target="_blank" >10.1016/j.ejmech.2020.112520</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and evaluation of Na⁺/K⁺-ATP-ase inhibiting and cytotoxic in vitro activities of oleandrigenin and its selected 17β-(butenolidyl)- and 17β-(3-furyl)- analogues

Popis výsledku v původním jazyce

Natural cardiac-active principles built upon the 14,16β-dihydroxy-5β,14β-androstane core and bearing a heterocyclic substituent at 17β, in particular, a cardenolide oleandrin and a bufadienolide bufotalin, are receiving a great deal of attention as potential anticancer drugs. The densely substituted and sterically shielded ring D is the particular structural feature of these compounds. The first synthesis of oleandrigenin from easily available steroid starting material is reported here. Furthermore, selected 17β-(4-butenolidyl)- and 17β-(3-furyl)-14,16β-dihydroxy-androstane derivatives were en route synthesized and examined for their Na+/K+-ATP-ase inhibitory properties as well as cytotoxic activities in normal and cancer cell lines. It was found that the furyl-analogue of oleandrigenin/bufatalin (7) and some related 17-(3-furyl)- derivatives (19, 21) show remarkably high Na+/K+-ATP-ase inhibitory activity as well as significant cytotoxicity in vitro. In addition, oleandrigenin 2 compared to derivatives 21 and 25 induced strong apoptosis in human cervical carcinoma HeLa cells after 24 h of treatment.

Název v anglickém jazyce

Synthesis and evaluation of Na⁺/K⁺-ATP-ase inhibiting and cytotoxic in vitro activities of oleandrigenin and its selected 17β-(butenolidyl)- and 17β-(3-furyl)- analogues

Popis výsledku anglicky

Natural cardiac-active principles built upon the 14,16β-dihydroxy-5β,14β-androstane core and bearing a heterocyclic substituent at 17β, in particular, a cardenolide oleandrin and a bufadienolide bufotalin, are receiving a great deal of attention as potential anticancer drugs. The densely substituted and sterically shielded ring D is the particular structural feature of these compounds. The first synthesis of oleandrigenin from easily available steroid starting material is reported here. Furthermore, selected 17β-(4-butenolidyl)- and 17β-(3-furyl)-14,16β-dihydroxy-androstane derivatives were en route synthesized and examined for their Na+/K+-ATP-ase inhibitory properties as well as cytotoxic activities in normal and cancer cell lines. It was found that the furyl-analogue of oleandrigenin/bufatalin (7) and some related 17-(3-furyl)- derivatives (19, 21) show remarkably high Na+/K+-ATP-ase inhibitory activity as well as significant cytotoxicity in vitro. In addition, oleandrigenin 2 compared to derivatives 21 and 25 induced strong apoptosis in human cervical carcinoma HeLa cells after 24 h of treatment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

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

202

Číslo periodika v rámci svazku

SEP 15

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

13

Strana od-do

112520

Kód UT WoS článku

000560369900017

EID výsledku v databázi Scopus

2-s2.0-85087430809