Structure-based virtual screening of Trachyspermum ammi metabolites targeting acetylcholinesterase for Alzheimer’s disease treatment

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0311401 - e0311401

Published: Dec. 17, 2024

In recent decades, Alzheimer’s disease (AD) has garnered significant attention due to its rapid global prevalence. The cholinergic hypothesis posits that the degradation of acetylcholine by acetylcholinesterase (AChE) contributes AD development. Despite existing anti-AChE drugs, their adverse side effects necessitate new agents. This study analyzed 150 bioactive phytochemicals from Trachyspermum ammi using structure-based drug design and various in-silico tools identify potent compounds. Compounds were screened for drug-likeness (QEDw ≥50%) bioavailability (≥55%) underwent toxicity profiling via ProTox-II server. Selected compounds prepared molecular docking with human AChE protein as receptor. Viridifloral, 2-Methyl-3-glucosyloxy-5-isopropyl phenol, Alpha-Curcumene, Sterol emerged top candidates high affinity. These results validated dynamics simulations, confirming stable interactions. hit further evaluated Lipinski’s rule ADMET properties, favorable pharmacokinetic profiles. DFT optimization frontier orbitals electrostatic potential, demonstrating chemical reactivity stability. suggests these identified could be novel nature-derived inhibitors, potentially contributing treatment. However, in-vitro in-vivo studies are necessary confirm efficacy in biological systems. Future research will focus on developing into safe effective drugs combat disease.

Language: Английский

Influence of Mg2+ and THF on THF-II riboswitch based on molecular dynamics simulations

Chemical Physics Letters, Journal Year: 2024, Volume and Issue: unknown, P. 141815 - 141815

Published: Dec. 1, 2024

Language: Английский