DFT Study of Regio- and Stereoselective 13DC Reaction between Diazopropane and Substituted Chalcone Derivatives: Molecular Docking of Novel Pyrazole Derivatives as Anti-Alzheimer's Agents

Sadeq M Al-Hazmy; Mohamed Oussama Zouaghi; Nasser Amri; Youssef Arfaoui; Ibrahim A Alhagri; Naceur Hamdi

doi:10.3390/molecules28041899

DFT Study of Regio- and Stereoselective 13DC Reaction between Diazopropane and Substituted Chalcone Derivatives: Molecular Docking of Novel Pyrazole Derivatives as Anti-Alzheimer's Agents

Molecules. 2023 Feb 16;28(4):1899. doi: 10.3390/molecules28041899.

Authors

Sadeq M Al-Hazmy¹, Mohamed Oussama Zouaghi², Nasser Amri³, Youssef Arfaoui², Ibrahim A Alhagri^{1

4}, Naceur Hamdi⁵

Affiliations

¹ Chemistry Department, College of Science, Qassim University, Buraidah 51452, Saudi Arabia.
² Laboratory of Characterizations, Applications and Modeling of Materials (LR18ES08), Department of Chemistry, Faculty of Sciences, University of Tunis El Manar, Tunis 2092, Tunisia.
³ Department of Chemistry, Faculty of Science, Jazan University, P.O. Box 2097, Jazan 45142, Saudi Arabia.
⁴ Department of Chemistry, College of Science, Ibb University, Ibb P.O. Box 70270, Yemen.
⁵ Department of Chemistry, College of Science and Arts, Qassim University, Ar Rass 52719, Saudi Arabia.

Abstract

In the present work, a combination of experimental and density functional theory (DFT) investigation of the (3+2) cycloaddition reactions of diazopropane with chalcone derivatives was reported. All calculations were performed using several DFT approaches (B3LYP, M06, M06-2X) and 6-311+G(d, p) basis set. Based on the NMR, MS analyses and IRC calculations, the pyrazole derivatives are the kinetic adducts over the oxadiazoles. The use of two equivalents of diazopropane leads to thermodynamical products. A molecular docking analysis was performed to investigate the efficiency of the obtained products against selected drug targets in anti-Alzheimer ligand-receptor interactions. We revealed that the ligands selected were bound mainly to the catalytic (CAS) and peripheral (PAS) anionic sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors, respectively. The selected ligands 1, 3, 4 and P14 may act as the best inhibitors against Alzheimer's disease (AD).

Keywords: 32CA; DFT; diazopropane; molecular docking; oxadiazoles; pyrazoles.

MeSH terms

Acetylcholinesterase / metabolism
Alzheimer Disease*
Butyrylcholinesterase / chemistry
Chalcone*
Chalcones* / chemistry
Cholinesterase Inhibitors / chemistry
Humans
Molecular Docking Simulation
Molecular Structure
Pyrazoles
Structure-Activity Relationship

Substances

Butyrylcholinesterase
Acetylcholinesterase
Chalcones
Chalcone
Cholinesterase Inhibitors
Pyrazoles

Grants and funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript except the suppot for the project number (QU-IF-4-5-1-28906) from Deputyship for Research& Innovation, Ministry of Education, Saudi Arabia.