Some phenolic compounds as inhibitors of glutathione s-transferase and glutathione reductase: an in vitro and in silico analysis

Pınar Güller

Makale detayları

Some phenolic compounds as inhibitors of glutathione s-transferase and glutathione reductase: an in vitro and in silico analysis

Yazarlar:

Pınar Güller

Yayıncı:

Ataturk University

Ana Başlıklar:

Biyolojik Olarak Aktif Moleküller | Biyomoleküler Modelleme ve Tasarım

Dergi:

Ata-Kimya Dergisi Vol.3 Issue 1, pp.31-37

Belge Tipi:

Makale

Yayın Tarihi:

6/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001291665

pISSN:

2822-3926

Anahtar kelimeler:

Özet:

 It has been determined that Glutathione S-transferases GSTs and Glutathione reductase GR activities increase in cancer cells and contribute to the progression of cancer by causing multidrug resistance MDR. Glutathione reductase catalyzes electron transfer between oxidized glutathione GSSG and nicotinamide adenine dinucleotide phosphate, reduced form, NADPH. The reduced glutathione GSH formed as a result of this reaction detoxifies various xenobiotics by attacking the electrophilic center in the catalysis of GSTs. Detoxification of anticancer drugs with increased expression of GST and GR in cancer cells reduces the effectiveness of these drugs. Therefore, GST and GR inhibition is an important approach in cancer treatments. In this study, from human erythrocytes, GR was isolated by using 2,5-ADP Sepharose 4B affinity chromatography method with 16.912 EUmg protein specific activity, and GST was isolated by using Glutathione Agarose affinity chromatography method with 4.88 EUmg protein specific activity. After the isolation of the enzymes, the inhibition effects of vanillin, epicatechin, and catechin on the activities were investigated. While all three substances did not inhibit GST, vanillin and epicatechin were found to inhibit GR with IC50 values of 86.25 μM and 345 μM, respectively. The elucidation of the inhibition mechanism was carried out by molecular docking studies using the AutoDock program.

 It has been determined that Glutathione S-transferases GSTs and Glutathione reductase GR activities increase in cancer cells and contribute to the progression of cancer by causing multidrug resistance MDR. Glutathione reductase catalyzes electron transfer between oxidized glutathione GSSG and nicotinamide adenine dinucleotide phosphate, reduced form, NADPH. The reduced glutathione GSH formed as a result of this reaction detoxifies various xenobiotics by attacking the electrophilic center in the catalysis of GSTs. Detoxification of anticancer drugs with increased expression of GST and GR in cancer cells reduces the effectiveness of these drugs. Therefore, GST and GR inhibition is an important approach in cancer treatments. In this study, from human erythrocytes, GR was isolated by using 2,5-ADP Sepharose 4B affinity chromatography method with 16.912 EUmg protein specific activity, and GST was isolated by using Glutathione Agarose affinity chromatography method with 4.88 EUmg protein specific activity. After the isolation of the enzymes, the inhibition effects of vanillin, epicatechin, and catechin on the activities were investigated. While all three substances did not inhibit GST, vanillin and epicatechin were found to inhibit GR with IC50 values of 86.25 μM and 345 μM, respectively. The elucidation of the inhibition mechanism was carried out by molecular docking studies using the AutoDock program.

 It has been determined that Glutathione S-transferases GSTs and Glutathione reductase GR activities increase in cancer cells and contribute to the progression of cancer by causing multidrug resistance MDR. Glutathione reductase catalyzes electron transfer between oxidized glutathione GSSG and nicotinamide adenine dinucleotide phosphate, reduced form, NADPH. The reduced glutathione GSH formed as a result of this reaction detoxifies various xenobiotics by attacking the electrophilic center in the catalysis of GSTs. Detoxification of anticancer drugs with increased expression of GST and GR in cancer cells reduces the effectiveness of these drugs. Therefore, GST and GR inhibition is an important approach in cancer treatments. In this study, from human erythrocytes, GR was isolated by using 2,5-ADP Sepharose 4B affinity chromatography method with 16.912 EUmg protein specific activity, and GST was isolated by using Glutathione Agarose affinity chromatography method with 4.88 EUmg protein specific activity. After the isolation of the enzymes, the inhibition effects of vanillin, epicatechin, and catechin on the activities were investigated. While all three substances did not inhibit GST, vanillin and epicatechin were found to inhibit GR with IC50 values of 86.25 μM and 345 μM, respectively. The elucidation of the inhibition mechanism was carried out by molecular docking studies using the AutoDock program.

 Glutatyon S-transferazlar GSTs ve Glutatyon redüktaz GR aktivitelerinin kanser hücresinde arttığı ve çoklu ilaç direncine MDR sebep olarak kanserin ilerlemesine katkıda bulunduğu belirlenmiştir. Glutatyon redüktaz okside glutatyon GSSG ile indirgenmiş nikotinamid adenin dinükleotid fosfat NADPH arasında elektron transferini katalize eder. Bu reaksiyon sonucu oluşan redükte glutatyon GSH GSTs katalizliğinde çeşitli ksenobiyotiklerin elektrofilik merkezine saldırarak detoksifiye eder. Kanser hücrelerinde antikanser ilaçların artan GST ve GR ekspresyonu ile detoksifikasyonu bu ilaçların etkinliğini azaltır. Bu nedenle kanser tedavilerinde GST ve GR inhibisyonu önemli bir yaklaşımdır. Bu çalışmada, insan eritrositlerinden GR izolasyonu 2,5-ADP Sepharose 4B afinite kromatografisi yöntemiyle 16,912 EÜmg protein spesifik aktiviteyle, GST izolasyonu ise Glutatyon Agaroz afinite kromatografisi yöntemiyle 4,88 EÜmg protein spesifik aktiviteyle gerçekleştirilmiştir. Enzimlerin izolasyonundan sonra vanilin, epikatekin ve katekinin aktiviteler üzerine inhibisyon etkisi incelenmiştir. Her üç madde de GSTyi inhibe etmezken, vanilin ve epikatekinin GRyi sırasıyla 86.25 µM ve 345 µM IC50 değerleriyle inhibe ettiği belirlenmiştir. İnhibisyon mekanizmasının aydınlatılması ise AutoDock programı kullanılarak moleküler yerleştirme çalışmaları ile gerçekleştirilmiştir.

Makale detayları

Some phenolic compounds as inhibitors of glutathione s-transferase and glutathione reductase: an in vitro and in silico analysis

Yazarlar:

Pınar Güller

Yayıncı:

Ataturk University

Ana Başlıklar:

Biyolojik Olarak Aktif Moleküller | Biyomoleküler Modelleme ve Tasarım

Dergi:

Ata-Kimya Dergisi Vol.3 Issue 1, pp.31-37

Belge Tipi:

Makale

Yayın Tarihi:

6/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001291665

pISSN:

2822-3926

Glutathione

vanillin

epicatechin

catechin

inhibition

molecular dockingGlutatyon

vanilin

epikatekin

katekin

inhibisyon

moleküler yerleştirme

Sayı

Makale detayları

Yazarlar: Pınar Güller

Yayıncı: Ataturk University

Ana Başlıklar: Biyolojik Olarak Aktif Moleküller | Biyomoleküler Modelleme ve Tasarım

Dergi: Ata-Kimya Dergisi Vol.3 Issue 1, pp.31-37

Belge Tipi: Makale

Yayın Tarihi: 6/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001291665

pISSN: 2822-3926

Sayı

Yazarlar:

Pınar Güller

Yayıncı:

Ataturk University

Ana Başlıklar:

Biyolojik Olarak Aktif Moleküller | Biyomoleküler Modelleme ve Tasarım

Dergi:

Ata-Kimya Dergisi Vol.3 Issue 1, pp.31-37

Belge Tipi:

Makale

Yayın Tarihi:

6/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001291665

pISSN:

2822-3926