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
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
Affiliations
Abdulhakeem S. Alamri
Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Majid Alhomrani
Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Walaa F. Alsanie
Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Hussain Alyami
College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Sonam Shakya
Department of Chemistry, Faculty of Science, Aligarh Muslim University, Aligarh 202002, India
Hamza Habeeballah
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences in Rabigh, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Abdulwahab Alamri
Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 55211, Saudi Arabia
Omar Alzahrani
School of Health and Biomedical Sciences, RMIT University, Melbourne 3001, Australia
Ahmed S. Alzahrani
Centre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Heba A. Alkhatabi
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Raed I. Felimban
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Abdulhameed Abdullah Alhabeeb
National Centre for Mental Health Promotion, P.O. Box 95459, Riyadh 11525, Saudi Arabia
Bassem M. Raafat
Department of Radiological Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Moamen S. Refat
Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Ahmed Gaber
Centre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
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.
