Page 102 - GPD-3-2

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Rational virtual screening, ADME, and molecular

simulation studies of potential inhibitors
of human superoxide dismutase 1 in a

dysfunctional antioxidant system

Ayodele Sunday Alonge 1 , Toluwase Hezekiah Fatoki * ,
2
Iseoluwa Isaac Ajayi 1 , Ibrahim Olabayode Saliu 3 , Stanley Chukwuejim 4 ,
Courage Dele Famusiwa 5 , Oluwafijimi Adetuyi 4 , and Ohunene Esther Joseph 1
1 Department of Biological Sciences, School of Life Science, Bamidele Olumilua University of
Education, Science and Technology, Ikere, Ekiti State, Nigeria
2 Applied Bioinformatics Laboratory, Department of Biochemistry, Faculty of Science, Federal
University Oye Ekiti, Oye, Ekiti State, Nigeria
3 Department of Genetics, School of Medicine, Washington University St. Louis, Missouri, United
States of America
4 Enzymology Laboratory, Department of Biochemistry, Faculty of Science, Federal University Oye
Ekiti, Oye, Ekiti State, Nigeria
5 Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry,
Faculty of Science, Federal University Oye Ekiti, Oye, Ekiti State, Nigeria

Abstract

*Corresponding author: Superoxide dismutase 1 (SOD1), a copper-dependent enzyme, facilitates the
Toluwase Hezekiah Fatoki
(toluwase.fatoki@fuoye.edu.ng) conversion of superoxide anions into hydrogen peroxide and oxygen, thereby

regulating superoxide levels. Dysfunctions in SOD1 have been linked to
Citation: Alonge AS, Fatoki TH,
Ajayi II, et al. Rational virtual neurodegenerative disorders such as amyotrophic lateral sclerosis, as well as liver and
screening, ADME, and molecular lung cancers. This study aimed to identify SOD1 modulators using in silico rational
simulation studies of potential virtual enrichment screening, pharmacokinetics, docking, and molecular dynamic
inhibitors of human superoxide
dismutase 1 in a dysfunctional simulation (MDS). The findings yielded 38 compounds, predominantly exhibiting
antioxidant system. Gene Protein Dis. high gastrointestinal absorption but mostly non-permeable across the blood–brain
2024;3(2):3042. barrier, with few exhibiting inhibitory effects on selected cytochrome P450s. Molecular
doi: 10.36922/gpd.3042
docking revealed that compound 1 (PubChem CID: 36791369) exhibited the highest
Received: February 28, 2024 binding affinity (−6.771 kcal·mol ), followed by compound 19 (PubChem CID: 30935)
-1
-1
Accepted: April 18, 2024 with −6.468 kcal·mol , and compound 20 (PubChem CID: 135744521) with −5.978
kcal·mol . MDS and molecular mechanics/generalized Born surface area analysis
-1
Published Online: June 5, 2024
indicated that the compound CID 36791369 – SOD1 complex and compound CID
Copyright: © 2024 Author(s). 30935 – SOD1 complex remained stable and energetically favorable under simulated
This is an Open Access article
distributed under the terms of the physiological conditions at 0 ns and 100 ns. In conclusion, this study identified 38
Creative Commons Attribution compounds, among which compounds SN5, SN6, SN7, SN12, and SN25 emerged
License, permitting distribution, as potential inhibitors of SOD1 based on overall analyses. Further, research will be
and reproduction in any medium,
provided the original work is necessary to investigate the therapeutic effectiveness of these top five compounds
properly cited. in vitro and in vivo against SOD1.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: SOD1; Cancer; Amyotrophic lateral sclerosis; Novel inhibitors;
regard to jurisdictional claims in
published maps and institutional Pharmacokinetics; Molecular docking; Molecular dynamics simulation
affiliations

Volume 3 Issue 2 (2024) 1 doi: 10.36922/gpd.3042