Unveiling the multitargeted potential of deprodone and control comparison with linezolid against hydrolase and transferase enzymes of methicillin-resistant Staphylococcus aureus.

Autor: Almufarriji FM; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah 19257, Riyadh, Saudi Arabia. Electronic address: falmufarriji@su.edu.sa., Alotaibi BS; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah 19257, Riyadh, Saudi Arabia. Electronic address: balotaibi@su.edu.sa., Alamri AS; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah 19257, Riyadh, Saudi Arabia. Electronic address: Ahlam@su.edu.sa., Alkhalil SS; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah 19257, Riyadh, Saudi Arabia. Electronic address: salkhalil@su.edu.sa., Alkhorayef N; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah 19257, Riyadh, Saudi Arabia. Electronic address: nalkhorayef@su.edu.sa., Hakami MA; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al-Quwayiyah 19257, Riyadh, Saudi Arabia. Electronic address: m.hakami@su.edu.sa.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Nov; Vol. 279 (Pt 3), pp. 135459. Date of Electronic Publication: 2024 Sep 07.
DOI: 10.1016/j.ijbiomac.2024.135459
Abstrakt: Staphylococcus aureus (S. aureus), commonly found on the skin and nose, causes minor skin conditions to life-threatening diseases, including boils or impetigo, pneumonia, and bloodstream infections. MRSA (Methicillin-Resistant S. aureus) is a strain resistant to many antibiotics and poses a significant challenge in clinical settings. Nowadays, the alternative drug Linezolid is used, and it is not clear when MRSA starts resistance to it, necessitating the need for more alternative drugs with the least chance of developing resistance. This study aims to identify a multitargeted drug candidate with better efficacy than Linezolid. We have taken three hydrolase and transferase proteins from S. aureus, performed the multitargeted docking studies with human-approved drugs, and compared them with the control drug Linezolid. The docking and MM\GBSA scores ranging from -6.79 to -5.78 Kcal/mol and - 37.47 to 30.16 Kcal/mol, respectively, that revealed Deprodone (used for inflammatory skin disorders, bowel disease, and fatty acid metabolism disorders) can be a far better and multitargeted drug candidate than Linezolid. We extended our studies to include extensive pharmacokinetics and molecular interaction fingerprints for interaction pattern studies. Also, the DFT computations optimised the drug, and we extended our studies for MD Simulation in water for 100 ns, which showed the complexes among the identified drug with proteins are entirely stable with acceptable deviation, fluctuations and many intermolecular interactions that make them stable. We also performed the MM\GBSA studies on MD simulation's all 1000 frames to understand the complex energy level. All the results reveal promising interactions between Deprodone and the targeted enzymes, suggesting its potential as a multitargeted therapeutic agent-however, experimental studies need to validate Deprodone against MRSA.
Competing Interests: Declaration of competing interest The authors declare no competing or conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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