Flavonolignan Conjugates as DNA-binding Ligands and Topoisomerase I Inhibitors: Electrochemical and Electrophoretic Approaches

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00467830" target="_blank" >RIV/68081707:_____/16:00467830 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/16:00467830 RIV/61989592:15110/16:33160665

Výsledek na webu

<a href="http://dx.doi.org/10.1002/elan.201600146" target="_blank" >http://dx.doi.org/10.1002/elan.201600146</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/elan.201600146" target="_blank" >10.1002/elan.201600146</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Flavonolignan Conjugates as DNA-binding Ligands and Topoisomerase I Inhibitors: Electrochemical and Electrophoretic Approaches

Popis výsledku v původním jazyce

In this work, the electrochemical behavior of flavonolignan silybin (SB) and 2,3-dehydrosilybin (DHSB) and their respective conjugates SB-SB and DHSB-DHSB were studied using voltammetric techniques at a glassy carbon electrode. The redox mechanism of SB and its conjugate occurs in two oxidation steps where the hydroxy groups of the guaiacyl and resorcinol moiety are involved. DHSB and its conjugate are oxidized in three subsequent steps. The enol group in DHSB and DHSB-DHSB is involved in the additional oxidation step, due to the enhanced electron-donor capacity and reactivity of the 2,3-dehydroderivatives compared to the parent flavonolignan molecule. The developed voltammetric methods were subsequently used for the analysis of flavonolignan-DNA interactions. Comparative experiments revealed a remarkable binding affinity between the flavonolignan homoconjugates and double-helical calf thymus DNA, compared to the corresponding monomeric compounds. In addition, biochemical and electrophoretic experiments revealed the flavonolignan-dsDNA binding not to involve intercalation as the major interaction mode. The same experiments have also shown that both flavonolignan conjugates inhibit the activity of type I topoisomerase, which is a DNA topology (superhelicity) modulating enzyme. We suppose that our results could be used in further studies focused on DNA flavonolignan binding and DNA processing protein inhibition by flavonolignan 2,3-dehydroderivatives.

Název v anglickém jazyce

Flavonolignan Conjugates as DNA-binding Ligands and Topoisomerase I Inhibitors: Electrochemical and Electrophoretic Approaches

Popis výsledku anglicky

In this work, the electrochemical behavior of flavonolignan silybin (SB) and 2,3-dehydrosilybin (DHSB) and their respective conjugates SB-SB and DHSB-DHSB were studied using voltammetric techniques at a glassy carbon electrode. The redox mechanism of SB and its conjugate occurs in two oxidation steps where the hydroxy groups of the guaiacyl and resorcinol moiety are involved. DHSB and its conjugate are oxidized in three subsequent steps. The enol group in DHSB and DHSB-DHSB is involved in the additional oxidation step, due to the enhanced electron-donor capacity and reactivity of the 2,3-dehydroderivatives compared to the parent flavonolignan molecule. The developed voltammetric methods were subsequently used for the analysis of flavonolignan-DNA interactions. Comparative experiments revealed a remarkable binding affinity between the flavonolignan homoconjugates and double-helical calf thymus DNA, compared to the corresponding monomeric compounds. In addition, biochemical and electrophoretic experiments revealed the flavonolignan-dsDNA binding not to involve intercalation as the major interaction mode. The same experiments have also shown that both flavonolignan conjugates inhibit the activity of type I topoisomerase, which is a DNA topology (superhelicity) modulating enzyme. We suppose that our results could be used in further studies focused on DNA flavonolignan binding and DNA processing protein inhibition by flavonolignan 2,3-dehydroderivatives.

Druh

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

CEP obor

CG - Elektrochemie

OECD FORD obor

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Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Electroanalysis

ISSN

1040-0397

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

9

Strana od-do

2866-2874

Kód UT WoS článku

000387891400032

EID výsledku v databázi Scopus

2-s2.0-84981328394