Structure-Based Discovery of Phytocompounds from Azadirachta indica as Potential Inhibitors of Thioredoxin Glutathione Reductase in Schistosoma mansoni.

Autor: Onile OS; Biotechnology Programme, Department of Biological Sciences, Elizade University, P.M.B 002, Ilara-Mokin, Ondo State, Nigeria. Olugbenga.onile@elizadeuniversity.edu.ng., Raji O; Biotechnology Programme, Department of Biological Sciences, Elizade University, P.M.B 002, Ilara-Mokin, Ondo State, Nigeria., Omoboyede V; Department of Biochemistry, School of Life Sciences (SLS), Federal University of Technology Akure, P.M.B 704, Akure, Nigeria., Fadahunsi AI; Biotechnology Programme, Department of Biological Sciences, Elizade University, P.M.B 002, Ilara-Mokin, Ondo State, Nigeria., Onile TA; Microbiology Programme, Department of Biological Sciences, Elizade University, P.M.B 002, Ilara-Mokin, Ondo State, Nigeria., Momoh AO; Microbiology Programme, Department of Biological Sciences, Elizade University, P.M.B 002, Ilara-Mokin, Ondo State, Nigeria., Olukunle S; Biotechnology Programme, Department of Biological Sciences, Elizade University, P.M.B 002, Ilara-Mokin, Ondo State, Nigeria., Nour H; Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, 7955, Morocco., Chtita S; Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, 7955, Morocco.
Jazyk: angličtina
Zdroj: Cell biochemistry and biophysics [Cell Biochem Biophys] 2024 Oct 07. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1007/s12013-024-01577-2
Abstrakt: Schistosomiasis, a parasitic disease caused by Schistosoma species such as S. haematobium, S. mansoni, and S. japonicum, poses a significant global health burden. The thioredoxin glutathione reductase (TGR) enzyme, crucial for maintaining the parasite's redox balance and preventing oxidative stress, has been identified as a promising target for anti-schistosomal drug development. This study aims to identify potential TGR inhibitors from Azadirachta indica phytochemicals using molecular modeling approaches. We screened 60 compounds derived from A. indica bark and leaves through molecular docking to assess their binding affinity, followed by the evaluation of binding-free energies for the most promising candidates. Drug-likeness and pharmacokinetic properties were assessed, and molecular dynamics simulations were conducted to explore the conformational stability of the protein-ligand complexes. Our findings revealed that several A. indica compounds exhibited significantly lower docking scores (up to -9.669 kcal/mol) compared to the standard drug praziquantel (-4.349 kcal/mol). Notably, Isorhamnetin, Isomargolonone, Nimbaflavone, Quercetin, and Nimbionol demonstrated strong interactions with TGR, although Isorhamnetin showed potential mutagenicity. Further binding free energy calculations and molecular dynamics simulations confirmed the stability of Isomargolonone, Nimbionol, and Quercetin as potential TGR inhibitors. In conclusion, these findings suggest that Isomargolonone, Nimbionol, and Quercetin warrant further experimental validation as promising candidates for anti-schistosomal therapy.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: