Chromone-isoxazole hybrids molecules: synthesis, spectroscopic, MEDT, ELF, antibacterial, ADME-Tox, molecular docking and MD simulation investigations

A mechanistic study was performed within the molecular electron density theory at the B3LYP/6-311G (d,p) computational level to explain the regioselectivity observed. An electron localization function analysis was also performed, and the results confirm the zwitterionic-type (zw-type) mechanism of t...

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Published in:Journal of biomolecular structure & dynamics 2024-08, Vol.42 (12), p.6410-6424
Main Authors: Kanzouai, Youssra, Laghmari, Mustapha, Yamari, Imane, Bouzammit, Rachid, Bahsis, Lahoucine, Benali, Taoufiq, Chtita, Samir, Bakhouch, Mohamed, Akhazzane, Mohamed, El Kouali, M'hammed, Hammani, Khalil, Al Houari, Ghali
Format: Article
Language:English
Subjects:
1,3-Dipolar cycloaddition
ADME-Tox
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Catalytic Domain
chromone-isoxazole
Chromones - chemical synthesis
Chromones - chemistry
Isoxazoles - chemistry
MEDT
Microbial Sensitivity Tests
Molecular Conformation
molecular docking
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular Structure
regioselectivity
Staphylococcus aureus - drug effects
Structure-Activity Relationship
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Summary:A mechanistic study was performed within the molecular electron density theory at the B3LYP/6-311G (d,p) computational level to explain the regioselectivity observed. An electron localization function analysis was also performed, and the results confirm the zwitterionic-type (zw-type) mechanism of the cycloaddition reactions between nitrile oxide and alkylated 4H-chromene-2-carboxylate derivatives and shed more light on the obtained regioselectivity experimentally. In silico studies on the pharmacokinetics, ADME and toxicity tests of the compounds were also performed, and it was projected that compounds 5a, 5b, 5c and 5d are pharmacokinetic and have favorable ADME profiles. Moreover, docking and molecular dynamics investigations were conducted to evaluate the interactions, orientation and conformation of the target compounds on the active sites of four distinct enzymes. The results of this investigation showed that two compounds, 5a and 5c, interacted effectively with the S. aureus active site while maintaining acceptable binding energy. Communicated by Ramaswamy H. Sarma
ISSN:0739-1102
1538-0254
1538-0254
DOI:10.1080/07391102.2023.2266022