Molecular Docking Assessment of Cathinones as 5-HT2AR Ligands: Developing of Predictive Structure-Based Bioactive Conformations and Three-Dimensional Structure-Activity Relationships Models for Future Recognition of Abuse Drugs(Article)(Open Access)
- aKragujevac Center for Computational Biochemistry, Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, P.O. Box 60, Kragujevac, 34000, Serbia
- bDepartment of Pharmacy, Faculty of Medicine, University of Niš, Bulevar Dr. Zorana Đinđića 81, Niš, 18000, Serbia
- cDepartment of Physics, Sri Chandrasekharendra Saraswathi Viswa Mahavidyalaya, Tamil Nadu, Kanchipuram, 631561, India
- dFaculty of Sciences and Mathematics, University of Niš, Višegradska 33, Niš, 18000, Serbia
- eDepartment of Science, Institute for Informational Technologies, University of Kragujevac, Jovana Cvijića bb, Kragujevac, 34000, Serbia
- fFaculty of Science and Mathematics, University of Montenegro, Džordža Vašingtona bb, Podgorica, 81000, Montenegro
- gDepartment of Drug Chemistry and Technology, Faculty of Pharmacy and Medicine, Rome Sapienza University, P.le A. Moro 5, Rome, 00185, Italy
- hRome Center for Molecular Design, Department of Drug Chemistry and Technology, Faculty of Pharmacy and Medicine, Rome Sapienza University, P.le A. Moro 5, Rome, 00185, Italy
Abstract
Commercially available cathinones are drugs of long-term abuse drugs whose pharmacology is fairly well understood. While their psychedelic effects are associated with 5-HT2AR, the enclosed study summarizes efforts to shed light on the pharmacodynamic profiles, not yet known at the receptor level, using molecular docking and three-dimensional quantitative structure–activity relationship (3-D QSAR) studies. The bioactive conformations of cathinones were modeled by AutoDock Vina and were used to build structure-based (SB) 3-D QSAR models using the Open3DQSAR engine. Graphical inspection of the results led to the depiction of a 3-D structure analysis-activity relationship (SAR) scheme that could be used as a guideline for molecular determinants by which any untested cathinone molecule can be predicted as a potential 5-HT2AR binder prior to experimental evaluation. The obtained models, which showed a good agreement with the chemical properties of co-crystallized 5-HT2AR ligands, proved to be valuable for future virtual screening campaigns to recognize unused cathinones and similar compounds, such as 5-HT2AR ligands, minimizing both time and financial resources for the characterization of their psychedelic effects. © 2023 by the authors.
Indexed keywords
| EMTREE drug terms: | cathinoneillicit drugligandpsychedelic agentserotonin |
|---|---|
| EMTREE medical terms: | molecular dockingquantitative structure activity relation |
| MeSH: | HallucinogensIllicit DrugsLigandsMolecular Docking SimulationQuantitative Structure-Activity RelationshipSerotonin |
Chemicals and CAS Registry Numbers:
cathinone, 5265-18-9, 71031-15-7, 77271-59-1; serotonin, 50-67-9;
cathinone; Hallucinogens; Illicit Drugs; Ligands; Serotonin
Funding details
| Funding sponsor | Funding number | Acronym |
|---|---|---|
| 451-03-47/2023-01/200378,451-03-47/2023-01/200122 | ||
| Sapienza Università di Roma | C26A15J3BB,C26A15RT82 | |
| 200122 |
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1
This work was supported by the Serbian Ministry of Science, Technological Development, and Innovation (Agreement Nos. 451-03-47/2023-01/200122 and 451-03-47/2023-01/200378), and supported by two grants from Progetti di Ricerca di Universit\u00E0 2015, Sapienza Universit\u00E0 di Roma (C26A15RT82 and C26A15J3BB).
- ISSN: 14203049
- CODEN: MOLEF
- Source Type: Journal
- Original language: English
- DOI: 10.3390/molecules28176236
- PubMed ID: 37687065
- Document Type: Article
- Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Tomašević, N.; Kragujevac Center for Computational Biochemistry, Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, P.O. Box 60, Kragujevac, Serbia;
Mladenović, M.; Kragujevac Center for Computational Biochemistry, Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, P.O. Box 60, Kragujevac, Serbia;
© Copyright 2023 Elsevier B.V., All rights reserved.
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