Determination of tyrosinase-cyanidin-3-O-glucoside and (-/ plus )-catechin binding modes reveal mechanistic differences in tyrosinase inhibition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F21%3A00551538" target="_blank" >RIV/86652036:_____/21:00551538 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41598-021-03569-1" target="_blank" >https://www.nature.com/articles/s41598-021-03569-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-021-03569-1" target="_blank" >10.1038/s41598-021-03569-1</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Determination of tyrosinase-cyanidin-3-O-glucoside and (-/ plus )-catechin binding modes reveal mechanistic differences in tyrosinase inhibition

Popis výsledku v původním jazyce

Tyrosinase, exquisitely catalyzes the phenolic compounds into brown or black pigment, inhibition is used as a treatment for dermatological or neurodegenerative disorders. Natural products, such as cyanidin-3-O-glucoside and (-/+)-catechin, are considered safe and non-toxic food additives in tyrosinase inhibition but their ambiguous inhibitory mechanism against tyrosinase is still elusive. Thus, we presented the mechanistic insights into tyrosinase with cyanidin-3-O-glucoside and (-/+)-catechin using computational simulations and in vitro assessment. Initial molecular docking results predicted ideal docked poses (- 9.346 to 5.795 kcal/mol) for tyrosinase with selected flavonoids. Furthermore, 100 ns molecular dynamics simulations and post-simulation analysis of docked poses established their stability and oxidation of flavonoids as substrate by tyrosinase. Particularly, metal chelation via catechol group linked with the free 3-OH group on the unconjugated dihydropyran heterocycle chain was elucidated to contribute to tyrosinase inhibition by (-/+)-catechin against cyanidin-3-O-glucoside. Also, predicted binding free energy using molecular mechanics/generalized Born surface area for each docked pose was consistent with in vitro enzyme inhibition for both mushroom and murine tyrosinases. Conclusively, (-/+)-catechin was observed for substantial tyrosinase inhibition and advocated for further investigation for drug development against tyrosinase-associated diseases.

Název v anglickém jazyce

Determination of tyrosinase-cyanidin-3-O-glucoside and (-/ plus )-catechin binding modes reveal mechanistic differences in tyrosinase inhibition

Popis výsledku anglicky

Tyrosinase, exquisitely catalyzes the phenolic compounds into brown or black pigment, inhibition is used as a treatment for dermatological or neurodegenerative disorders. Natural products, such as cyanidin-3-O-glucoside and (-/+)-catechin, are considered safe and non-toxic food additives in tyrosinase inhibition but their ambiguous inhibitory mechanism against tyrosinase is still elusive. Thus, we presented the mechanistic insights into tyrosinase with cyanidin-3-O-glucoside and (-/+)-catechin using computational simulations and in vitro assessment. Initial molecular docking results predicted ideal docked poses (- 9.346 to 5.795 kcal/mol) for tyrosinase with selected flavonoids. Furthermore, 100 ns molecular dynamics simulations and post-simulation analysis of docked poses established their stability and oxidation of flavonoids as substrate by tyrosinase. Particularly, metal chelation via catechol group linked with the free 3-OH group on the unconjugated dihydropyran heterocycle chain was elucidated to contribute to tyrosinase inhibition by (-/+)-catechin against cyanidin-3-O-glucoside. Also, predicted binding free energy using molecular mechanics/generalized Born surface area for each docked pose was consistent with in vitro enzyme inhibition for both mushroom and murine tyrosinases. Conclusively, (-/+)-catechin was observed for substantial tyrosinase inhibition and advocated for further investigation for drug development against tyrosinase-associated diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10700 - Other natural sciences

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Svazek periodika

11

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

25

Strana od-do

24494

Kód UT WoS článku

000736780900007

EID výsledku v databázi Scopus

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