Enhancing the Antipsychotic Effect of Risperidone by Increasing Its Binding Affinity to Serotonin Receptor via Picric Acid: A Molecular Dynamics Simulation

Majid Alhomrani; Walaa F Alsanie; Abdulhakeem S Alamri; Hussain Alyami; Hamza Habeeballah; Heba A Alkhatabi; Raed I Felimban; John M Haynes; Sonam Shakya; Bassem M Raafat; Moamen S Refat; Ahmed Gaber

doi:10.3390/ph15030285

Enhancing the Antipsychotic Effect of Risperidone by Increasing Its Binding Affinity to Serotonin Receptor via Picric Acid: A Molecular Dynamics Simulation

Pharmaceuticals (Basel). 2022 Feb 24;15(3):285. doi: 10.3390/ph15030285.

Authors

Majid Alhomrani^{1

2}, Walaa F Alsanie^{1

2}, Abdulhakeem S Alamri^{1

2}, Hussain Alyami³, Hamza Habeeballah⁴, Heba A Alkhatabi^{5

6

7}, Raed I Felimban^{5

8}, John M Haynes⁹, Sonam Shakya¹⁰, Bassem M Raafat¹¹, Moamen S Refat¹², Ahmed Gaber^{2

13}

Affiliations

¹ Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
² Centre of Biomedical Sciences Research (CBSR), Deanship of Scientific Research, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
³ College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁴ Faculty of Applied Medical Sciences in Rabigh, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁷ Hematology Research Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁸ Center of Innovation in Personalized Medicine (CIPM), 3D Bioprinting Unit, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁹ Monash Institute of Pharmaceutical Sciences, 381 Royal Parade Parkville, Melbourne, VIC 3052, Australia.
¹⁰ Department of Chemistry, Faculty of Science, Aligarh Muslim University, Aligarh 202002, India.
¹¹ Department of Radiological Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
¹² Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
¹³ Department of Biology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

The aim of this study was to assess the utility of inexpensive techniques in evaluating the interactions of risperidone (Ris) with different traditional π-acceptors, with subsequent application of the findings into a Ris pharmaceutical formulation with improved therapeutic properties. Molecular docking calculations were performed using Ris and its different charge-transfer complexes (CT) with picric acid (PA), 2,3-dichloro-5,6-dicyanop-benzoquinon (DDQ), tetracyanoquinodimethane (TCNQ), tetracyano ethylene (TCNE), tetrabromo-pquinon (BL), and tetrachloro-p-quinon (CL), as donors, and three receptors (serotonin, dopamine, and adrenergic) as acceptors to study the comparative interactions among them. To refine the docking results and further investigate the molecular processes of receptor-ligand interactions, a molecular dynamics simulation was run with output obtained from AutoDock Vina. Among all investigated complexes, the [(Ris) (PA)]-serotonin (CTcS) complex showed the highest binding energy. Molecular dynamics simulation of the 100 ns run revealed that both the Ris-serotonin (RisS) and CTcS complexes had a stable conformation; however, the CTcS complex was more stable.

Keywords: antipsychotic drug; charge-transfer complexes; molecular docking; risperidone.

Grants and funding

1-441-120/Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia