Stress degradation, structural optimization, molecular docking, ADMET analysis of tiemonium methylsulphate and its degradation products

Abstract

Attempts have been taken to study stress degradation of tiemonium methylsulphate (TMS). Quantum mechanical approach was applied to investigate the structural information, protein binding affinity and pharmacokinetic properties of the TMS and degradation products. Forced degradation study revealed that TMS degraded significantly under acid hydrolysis and photolytic degradation conditions than basic, thermal or oxidative conditions. Density functional theory (DFT) with B3LYP/6-31G+ (d, p) has been employed to optimize the structures. Frontier molecular orbital features (HOMO-LUMO) gap, hardness, softness), dipole moment, atomic partial charge, electrostatic potential and thermodynamic properties (electronic energy, enthalpy, Gibb's free energy) are investigated for optimization of degradation products. Molecular docking has been performed against muscarinic acetylcholine receptor protein 5DSG to search the binding affinity and mode(s). ADMET calculation predicts that all the products are non-carcinogenic and safe for oral administration.

Computational and Pharmacokinetic Investigation of Some Heterocyclic Amide Derivatives as Cyclooxygenase Inhibitors: An In-Silico Approach

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“…Larger values relate to the more possible bindings while the negative sign indicates the spontaneous binding. 30,46,47 There is no external energy required for bindings because all of the compound's free energy and enthalpy values are negative (Table 1). In comparison to the other amide derivatives, the higher electronegative atoms fluorine and oxygen contained in compounds 4 and 6 also have a higher energy value.…”

Modification of ibuprofen to improve the medicinal effect; structural, biological, and toxicological study

“…Additionally, π-systems hold importance in ligand-protein recognition within biological phenomena. In biological systems, π-bonds contribute substantially to the binding energy [ 62 , 63 ]. In our investigation, nearly all complexes have exhibited Pi-Alkyl interactions with significant amino acid residues.…”

Comparative assessment of some benzodiazepine drugs based on Density Functional Theory, molecular docking, and ADMET studies

“…The 3D crystal structure of the human gamma-aminobutyric acid receptor protein (PDB ID: 4COF) was collected from the online protein data bank (PDB) database [17]. To overcome improper bond order, chain geometry disorder, missing hydrogen atoms; the structure was checked and prepared by PyMOL (Educational version 1.7.4), and Swiss-Pdb viewer software (Version 4.1.0) was utilized for energy minimization [18,19]. Finally, the optimized drugs were subjected to molecular docking study against the human GABAA receptor protein (4COF) considering the protein as a macromolecule and the drug as ligand.…”