Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer

Ani Fatonah, Usman Sumo Friend Tambunan, Wilis Okti Pamungkas, Gana Lahirin Dewanto, Ig Satrio Wicaksono

Research output: Contribution to journalArticle

Abstract

As one of the most complex diseases in the world, cancer continues as one of the significant public health problems. It was recorded by 2014 that cancer caused 1,551,000 death in Indonesia. One type of programmed cell death (PCD) that played a role in cancer cell treatment is Ferroptosis. Ferroptosis is PCD on iron and characterized by the inactivation of glutathione-dependent peroxidase (GPx4). In this research, a new therapeutic strategy for cancer was developed through the computational approach on synthetic compounds to discover its potential as an inhibitor of GPx4. About 688 compounds derivative from mercaptosuccinic acid acquired from the Zinc15 database. These compounds screened through the Lipinski’s Rule of Three and pharmacological prediction to eliminate ligands with undesired molecular properties. After that, the ligands underwent both rigid and flexible molecular docking simulations to predict their inhibition activity toward GPx4. From molecular docking simulation, (2S)-2-[(Z)-3-phenylprop-2-enyl]sulfanylbutanedioic acid show favorable characteristics as a drug candidate.

Original languageEnglish
Pages (from-to)4929-4933
Number of pages5
JournalBiointerface Research in Applied Chemistry
Volume10
Issue number1
DOIs
Publication statusPublished - 15 Feb 2020

Fingerprint

Molecular Docking Simulation
Cell death
Ligands
Public health
Medical problems
Peroxidase
Glutathione
Neoplasms
Cell Death
Iron
Cells
Derivatives
Acids
Indonesia
Glutathione Peroxidase
Pharmaceutical Preparations
Public Health
Databases
Pharmacology
Research

Keywords

  • Cancer
  • Ferroptosis
  • GPx4
  • Mercaptosuccinic Acid
  • Molecular Docking Simulation

Cite this

Fatonah, Ani ; Tambunan, Usman Sumo Friend ; Pamungkas, Wilis Okti ; Dewanto, Gana Lahirin ; Wicaksono, Ig Satrio. / Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer. In: Biointerface Research in Applied Chemistry. 2020 ; Vol. 10, No. 1. pp. 4929-4933.
@article{d85be957a6444a308735c9b928a9581f,
title = "Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer",
abstract = "As one of the most complex diseases in the world, cancer continues as one of the significant public health problems. It was recorded by 2014 that cancer caused 1,551,000 death in Indonesia. One type of programmed cell death (PCD) that played a role in cancer cell treatment is Ferroptosis. Ferroptosis is PCD on iron and characterized by the inactivation of glutathione-dependent peroxidase (GPx4). In this research, a new therapeutic strategy for cancer was developed through the computational approach on synthetic compounds to discover its potential as an inhibitor of GPx4. About 688 compounds derivative from mercaptosuccinic acid acquired from the Zinc15 database. These compounds screened through the Lipinski’s Rule of Three and pharmacological prediction to eliminate ligands with undesired molecular properties. After that, the ligands underwent both rigid and flexible molecular docking simulations to predict their inhibition activity toward GPx4. From molecular docking simulation, (2S)-2-[(Z)-3-phenylprop-2-enyl]sulfanylbutanedioic acid show favorable characteristics as a drug candidate.",
keywords = "Cancer, Ferroptosis, GPx4, Mercaptosuccinic Acid, Molecular Docking Simulation",
author = "Ani Fatonah and Tambunan, {Usman Sumo Friend} and Pamungkas, {Wilis Okti} and Dewanto, {Gana Lahirin} and Wicaksono, {Ig Satrio}",
year = "2020",
month = "2",
day = "15",
doi = "10.33263/BRIAC101.929933",
language = "English",
volume = "10",
pages = "4929--4933",
journal = "Biointerface Research in Applied Chemistry",
issn = "2069-5837",
publisher = "AMG Transcend Association",
number = "1",

}

Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer. / Fatonah, Ani; Tambunan, Usman Sumo Friend; Pamungkas, Wilis Okti; Dewanto, Gana Lahirin; Wicaksono, Ig Satrio.

In: Biointerface Research in Applied Chemistry, Vol. 10, No. 1, 15.02.2020, p. 4929-4933.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer

AU - Fatonah, Ani

AU - Tambunan, Usman Sumo Friend

AU - Pamungkas, Wilis Okti

AU - Dewanto, Gana Lahirin

AU - Wicaksono, Ig Satrio

PY - 2020/2/15

Y1 - 2020/2/15

N2 - As one of the most complex diseases in the world, cancer continues as one of the significant public health problems. It was recorded by 2014 that cancer caused 1,551,000 death in Indonesia. One type of programmed cell death (PCD) that played a role in cancer cell treatment is Ferroptosis. Ferroptosis is PCD on iron and characterized by the inactivation of glutathione-dependent peroxidase (GPx4). In this research, a new therapeutic strategy for cancer was developed through the computational approach on synthetic compounds to discover its potential as an inhibitor of GPx4. About 688 compounds derivative from mercaptosuccinic acid acquired from the Zinc15 database. These compounds screened through the Lipinski’s Rule of Three and pharmacological prediction to eliminate ligands with undesired molecular properties. After that, the ligands underwent both rigid and flexible molecular docking simulations to predict their inhibition activity toward GPx4. From molecular docking simulation, (2S)-2-[(Z)-3-phenylprop-2-enyl]sulfanylbutanedioic acid show favorable characteristics as a drug candidate.

AB - As one of the most complex diseases in the world, cancer continues as one of the significant public health problems. It was recorded by 2014 that cancer caused 1,551,000 death in Indonesia. One type of programmed cell death (PCD) that played a role in cancer cell treatment is Ferroptosis. Ferroptosis is PCD on iron and characterized by the inactivation of glutathione-dependent peroxidase (GPx4). In this research, a new therapeutic strategy for cancer was developed through the computational approach on synthetic compounds to discover its potential as an inhibitor of GPx4. About 688 compounds derivative from mercaptosuccinic acid acquired from the Zinc15 database. These compounds screened through the Lipinski’s Rule of Three and pharmacological prediction to eliminate ligands with undesired molecular properties. After that, the ligands underwent both rigid and flexible molecular docking simulations to predict their inhibition activity toward GPx4. From molecular docking simulation, (2S)-2-[(Z)-3-phenylprop-2-enyl]sulfanylbutanedioic acid show favorable characteristics as a drug candidate.

KW - Cancer

KW - Ferroptosis

KW - GPx4

KW - Mercaptosuccinic Acid

KW - Molecular Docking Simulation

UR - http://www.scopus.com/inward/record.url?scp=85077842541&partnerID=8YFLogxK

U2 - 10.33263/BRIAC101.929933

DO - 10.33263/BRIAC101.929933

M3 - Article

AN - SCOPUS:85077842541

VL - 10

SP - 4929

EP - 4933

JO - Biointerface Research in Applied Chemistry

JF - Biointerface Research in Applied Chemistry

SN - 2069-5837

IS - 1

ER -