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Enhancement of Haloperidol Binding Affinity to Dopamine Receptor via Forming a Charge-Transfer Complex with Picric Acid and 7,7,8,8-Tetracyanoquinodimethane for Improvement of the Antipsychotic Efficacy

Authors :
Abdulhakeem S. Alamri
Majid Alhomrani
Walaa F. Alsanie
Hussain Alyami
Sonam Shakya
Hamza Habeeballah
Abdulwahab Alamri
Omar Alzahrani
Ahmed S. Alzahrani
Heba A. Alkhatabi
Raed I. Felimban
Abdulhameed Abdullah Alhabeeb
Bassem M. Raafat
Moamen S. Refat
Ahmed Gaber
Source :
Molecules; Volume 27; Issue 10; Pages: 3295
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Haloperidol (HPL) is a typical antipsychotic drug used to treat acute psychotic conditions, delirium, and schizophrenia. Solid charge transfer (CT) products of HPL with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have not been reported till date. Therefore, we conducted this study to investigate the donor–acceptor CT interactions between HPL (donor) and TCNQ and PA (π-acceptors) in liquid and solid states. The complete spectroscopic and analytical analyses deduced that the stoichiometry of these synthesized complexes was 1:1 molar ratio. Molecular docking calculations were performed for HPL as a donor and the resulting CT complexes with TCNQ and PA as acceptors with two protein receptors, serotonin and dopamine, to study the comparative interactions among them, as they are important neurotransmitters that play a large role in mental health. A molecular dynamics simulation was ran for 100 ns with the output from AutoDock Vina to refine docking results and better examine the molecular processes of receptor–ligand interactions. When compared to the reactant donor, the CT complex [(HPL)(TCNQ)] interacted with serotonin and dopamine more efficiently than HPL only. CT complex [(HPL)(TCNQ)] with dopamine (CTtD) showed the greatest binding energy value among all. Additionally, CTtD complex established more a stable interaction with dopamine than HPL–dopamine.

Details

ISSN :
14203049
Volume :
27
Database :
OpenAIRE
Journal :
Molecules
Accession number :
edsair.doi.dedup.....d4c02aa9a1202e2a3f4e79aeb957af05
Full Text :
https://doi.org/10.3390/molecules27103295