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
Nevena Tomašević, Maja Vujović, E. Kostić, V. Ragavendran, Biljana Arsić, Sanja Matić, Mijat Božović, Rossella Fioravanti, Eleonora Proia, Rino Ragno, Milan Mladenović
Molecules August 24, 2023 DOI: 10.3390/molecules28176236 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or computational modeling study Peer reviewed |
|---|---|
| Topics | Serotonin |
| Citations | 5 |
| Key points | The authors report that structure-based 3-D QSAR models of cathinone binding to the 5-HT2A receptor, built from AutoDock Vina conformations, agreed with the chemical properties of co-crystallized 5-HT2A ligands. They propose a 3-D structure-activity relationship scheme as a guideline for predicting untested cathinones as potential 5-HT2A binders and for virtual screening. |
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.
Comparable studies
Other theoretical and historical papers on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics as Medicines: An Emerging New Paradigm General population | 2016 | Theoretical or philosophical paper | |
| Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate | 2018 | Theoretical or philosophical paper | |
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Dreams, Hallucinogenic Drug States, and Schizophrenia: A Psychological and Biological Comparison | 1983 | Theoretical or philosophical paper | |
| Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract. | 2022 | Theoretical or philosophical paper |
Citations in the library
Cited by 2
- A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics Biology October 28, 2023
- Potential Serotonin 5-HT2A Receptor Agonist of Psychoactive Components of Silene undulata Aiton: LC-MS/MS, ADMET, and Molecular Docking Studies. Current Pharmaceutical Biotechnology 2025
Cites 11
- Structural Features for Functional Selectivity at Serotonin Receptors Science March 21, 2013
- Crystal structure of an LSD-bound human serotonin receptor Cell January 26, 2017
- Structure-based discovery of nonhallucinogenic psychedelic analogs Science January 27, 2022
- Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways Current Topics in Behavioral Neurosciences 2017
- Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. Neuron October 5, 2022
and 6 more in the library