Molecular Docking Assessment of Cathinones as 5-HT<sub>2A</sub>R 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,
Emilija Kostić,
Venkatesan Ragavendran,
Biljana Arsić,
Sanja Lj. Matić,
Mijat Božović,
Rossella Fioravanti,
Eleonora Proia,
Rino Ragno,
Milan Mladenović
Affiliations
Nevena Tomašević
Kragujevac Center for Computational Biochemistry, Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, P.O. Box 60, 34000 Kragujevac, Serbia
Maja Vujović
Department of Pharmacy, Faculty of Medicine, University of Niš, Bulevar Dr. Zorana Đinđića 81, 18000 Niš, Serbia
Emilija Kostić
Department of Pharmacy, Faculty of Medicine, University of Niš, Bulevar Dr. Zorana Đinđića 81, 18000 Niš, Serbia
Venkatesan Ragavendran
Department of Physics, Sri Chandrasekharendra Saraswathi Viswa Mahavidyalaya, Kanchipuram 631561, Tamil Nadu, India
Biljana Arsić
Faculty of Sciences and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia
Sanja Lj. Matić
Department of Science, Institute for Informational Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia
Mijat Božović
Faculty of Science and Mathematics, University of Montenegro, Džordža Vašingtona bb, 81000 Podgorica, Montenegro
Rossella Fioravanti
Department of Drug Chemistry and Technology, Faculty of Pharmacy and Medicine, Rome Sapienza University, P.le A. Moro 5, 00185 Rome, Italy
Eleonora Proia
Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Faculty of Pharmacy and Medicine, Rome Sapienza University, P.le A. Moro 5, 00185 Rome, Italy
Rino Ragno
Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Faculty of Pharmacy and Medicine, Rome Sapienza University, P.le A. Moro 5, 00185 Rome, Italy
Milan Mladenović
Kragujevac Center for Computational Biochemistry, Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, P.O. Box 60, 34000 Kragujevac, Serbia
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.
