Oleanolic acid purified from the stem bark of Olax subscorpioidea Oliv. inhibits the function and catalysis of human 17β-hydroxysteroid dehydrogenase 1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F25%3A00641551" target="_blank" >RIV/61389030:_____/25:00641551 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/24:73627874

Výsledek na webu

<a href="https://doi.org/10.1080/07391102.2024.2423173" target="_blank" >https://doi.org/10.1080/07391102.2024.2423173</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2024.2423173" target="_blank" >10.1080/07391102.2024.2423173</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Oleanolic acid purified from the stem bark of Olax subscorpioidea Oliv. inhibits the function and catalysis of human 17β-hydroxysteroid dehydrogenase 1

Popis výsledku v původním jazyce

Cancer is a leading cause of global death. Medicinal plants have gained increasing attention in cancer drug discovery. In this study, the stem bark extract of Olax subscorpioidea, which is used in ethnomedicine to treat cancer, was subjected to phytochemical investigation leading to the isolation of oleanolic acid (OA). The structure was elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopic (NMR) data, and by comparing its data with previously reported data. Molecular docking was used to investigate the interactions of OA with nine selected cancer-related protein targets. OA docked well with human 17 beta-hydroxysteroid dehydrogenase type-1 (17 beta HSD1), caspase-3, and epidermal growth factor receptor tyrosine kinase (binding affinities:9.8,9.3, and9.1 kcal/mol, respectively). OA is a triterpenoid compound with structural similarity to steroids. This similarity with the substrates of 17 beta HSD1 gives the inhibitor candidate an excellent opportunity to bind to 17 beta HSD1. The structural and functional dynamics of OA-17 beta HSD1 were investigated by molecular dynamics simulations at 240 ns. Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) studies showed that OA had a binding free energy that is comparable with that of vincristine (-52.76, and63.56 kcal/mol, respectively). The average C-alpha root mean square of deviation (RMSD) value of OA (1.69 & Aring) compared with the unbound protein (2.01 & Aring) indicated its high stability at the protein's active site. The binding energy and stability at the active site of 17 beta HSD1 recorded in this study indicate that OA exhibited profound inhibitory potential. OA could be a good scaffold for developing new anti-breast cancer drugs.

Název v anglickém jazyce

Oleanolic acid purified from the stem bark of Olax subscorpioidea Oliv. inhibits the function and catalysis of human 17β-hydroxysteroid dehydrogenase 1

Popis výsledku anglicky

Cancer is a leading cause of global death. Medicinal plants have gained increasing attention in cancer drug discovery. In this study, the stem bark extract of Olax subscorpioidea, which is used in ethnomedicine to treat cancer, was subjected to phytochemical investigation leading to the isolation of oleanolic acid (OA). The structure was elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopic (NMR) data, and by comparing its data with previously reported data. Molecular docking was used to investigate the interactions of OA with nine selected cancer-related protein targets. OA docked well with human 17 beta-hydroxysteroid dehydrogenase type-1 (17 beta HSD1), caspase-3, and epidermal growth factor receptor tyrosine kinase (binding affinities:9.8,9.3, and9.1 kcal/mol, respectively). OA is a triterpenoid compound with structural similarity to steroids. This similarity with the substrates of 17 beta HSD1 gives the inhibitor candidate an excellent opportunity to bind to 17 beta HSD1. The structural and functional dynamics of OA-17 beta HSD1 were investigated by molecular dynamics simulations at 240 ns. Molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) studies showed that OA had a binding free energy that is comparable with that of vincristine (-52.76, and63.56 kcal/mol, respectively). The average C-alpha root mean square of deviation (RMSD) value of OA (1.69 & Aring) compared with the unbound protein (2.01 & Aring) indicated its high stability at the protein's active site. The binding energy and stability at the active site of 17 beta HSD1 recorded in this study indicate that OA exhibited profound inhibitory potential. OA could be a good scaffold for developing new anti-breast cancer drugs.

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

2025

Kód důvěrnosti údajů

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

Název periodika

Journal of Biomolecular Structure & Dynamics

ISSN

0739-1102

e-ISSN

1538-0254

Svazek periodika

43

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

7949-7962

Kód UT WoS článku

001347002200001

EID výsledku v databázi Scopus

2-s2.0-85209072213