Substituted piperidine as a novel lead molecule for the treatment of Parkinson's disease: Synthesis, crystal structure, hirshfeld surface analysis, and molecular modeling

Abstract

The current research outlines the synthesis of benzyl 4- (4-chlorophenylamino) -1-(4-chlorophenyl) -2,6-bis(4-chlorophenyl) -1,2,5,6-tetrahydropyridine -3-carboxylate. The title compound was crystallized in the monoclinic space group P21/n with Z = 4 and unit cell parameters a = 13.6684 Å (8), b = 9.1256 Å (4), c = 14.0839 Å (8), = 111.168 (7)°, and V = 1638.18 (17)°. The six-membered non-planar ring is shaped like a boat. Intermolecular C–H···Cl hydrogen bonds connect molecules in a three-dimensional crystal framework. The most significant contributions to crystal packing, according to the Hirshfeld surface investigation of the crystal structure, are from H ··· H (35.3%), H... Cl/Cl... H (27.0%), and H ··· C/C ··· H (21.8%). As a result, van der Waals interactions take precedence in crystal packing. In-vitro studies suggested this compound has better IC50 value of 0.588 ± 0.09 µM against MAO-A. In silico investigations, such as molecular docking, demonstrated that this molecule possessed exceptionally high Monoamine Oxidase A and Monoamine Oxidase B activity, with a binding energy value of -32.504 kJ/mol. Furthermore, Density functional theory (DFT) analyses supported these findings and suggested derivative 4 as a potential 'lead' molecule in pharmaceutical discovery and development.