Exploring Highly Functionalized Tetrahydropyridine as a Dual Inhibitor of Monoamine Oxidase A and B: Synthesis, Structural Analysis, Single Crystal XRD, Supramolecular Assembly Exploration by Hirshfeld Surface Analysis, and Computational Studies

Ethyl 4-(4-fluorophenylamino)-2,6-bis­(4-(trifluoromethyl)­phenyl)-1-(4-fluoro-phenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate
(FTEAA) has been synthesized efficiently in an iodine-catalyzed
five-component reaction of 4-fluoroaniline, 4-trifluoromethyl benzaldehyde,
and ethyl acetoacetate in methanol at 55 °C for 12 h. Various
spectro-analytical techniques such as 1H and 13C NMR and Fourier-transform infrared spectroscopy have validated
the structure of FTEAA. Further confirmation of the structure
of FTEAA has been established on the basis of single-crystal
X-ray diffraction analysis. The supramolecular assembly of FTEAA in terms of strong and comparatively weak noncovalent interactions
is fully investigated by Hirshfeld surface analysis, the interaction
energy between pairs of molecules, and energy frameworks. The void
analysis is conducted to explore the strength and stability of the
crystal structure. Furthermore, molecular docking analysis was computationally
performed to see the potential intermolecular interactions between
the selected proteins and FTEAA. The binding interaction
energies are found to be −8.8 and −9.6 kcal/mol for
the proteins MAO-B (PDB ID: 2V5Z) and MAO-A (PDB ID: 2Z5X), respectively. These reasonably good
binding energies (more negative values) indicate the efficient associations
between the FTEAA and target proteins. The proteins and FTEAA were also analyzed for intermolecular interactions. FTEAA and proteins interact in a variety of ways, like conventional
hydrogen bonds, carbon–hydrogen bonds, alkyl, π-alkyl,
and halide interactions.