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Investigating dimethyl fumarate derivatives as drugs against oxidative stress using the molecular docking with KEAP1 protein
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Saeedreza Emamian1   , Javad Hosseini2  , Safa Ali-Asgari2 |
1- Associate Professor, Department of Chemistry and Biochemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran , saeedreza_em@yahoo.com
2- Assistant Professor, Department of Chemistry and Biochemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran |
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Abstract: (4 Views) |
Abstract
Background: Oxidative stress is the starting point of many chronic diseases, including diabetes, cancer, and the cause of Alzheimer's, Parkinson's, and multiple sclerosis. KEAP1-NRF2 pathway is the principal protective response to oxidative and electrophilic stresses. The presence of KEAP1-NRF2 system in multiple cellular and metabolic message pathways suggests NRF2 activation as a critical regulatory factor in many disease phenotypes. In this research, the molecular docking of DMF and its three derivatives DMNBF, DMCBF and DMBBF with Keap1 protein to activate NRF2 with the aim of dealing with oxidative and electrophilic stresses was investigated.
Materials and methods: The affinity energy value for DMF and its three derivatives, DMNBF, DMCBF and DMBBF, with Keap1 protein in the three active regions of the protein was calculated using the molecular docking method and the type of interactions was determined.
Results: The results showed that DMNBF binds to Keap1 protein with affinity energy of 5.9, 5.7 and 3.7 kcal in all three active regions more effectively than DMF and other derivatives.
Conclusion: DMF is an approved drug for the treatment of psoriasis and multiple sclerosis. It interacts with Keap1 to activation of NRF2 in order to protective response against oxidative stress. Similarly, the DMNBF molecule may be able to be studied in lower doses and with fewer side effects for the treatment of psoriasis and multiple sclerosis or for the activation of NRF2 in the treatment of diseases that are somehow related to the KEAP1-NRF2 system |
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| Keywords: Molecular docking, Oxidative stress, Reactive oxygen species, KEAP1-NRF2 pathway, Dimethyl fumarate derivatives |
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Full-Text [PDF 1379 kb]
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Semi-pilot: Basic |
Subject:
Molecular Biology
Received: 2024/11/19 | Accepted: 2025/01/21 | Published: 2025/12/1
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