Spectral Investigations, DFT Studies, ADME Analysis, Molecular Docking of New Piperidine Derivatives with Potential Antimicrobial Activity

Abstract

Objective: To explore the possibility of obtaining effective and harmless antibacterial drugs by conventional synthesis of new piperidine analogs. Methods: The target compound was carried out by cyclization reaction involving aromatic aldehydes and amine and further evaluated for their antimicrobiological assay using agar disc diffusion method. Computational investigation such as density functional theory (DFT) was carried out by B3LYP/6-31G (d,p) method to evaluate their electronic characteristics. Absorption, Distribution, Metabolism, and Excretion (ADME) properties were evaluated using the Swiss ADME server. The Antimicrobial activity was investigated using molecular docking and that molecule was prepared using MGL Tools 1.5.7. Auto Dock Vina 1.2.0. Findings: Among all the synthesized compounds 5a to 5h, compounds 5b and 5e showed good anti-bacterial properties against three pathogenic bacterial strains. B. subtilis is inhibited by compound 5b at a concentration of 26 mm. B. subtilis is inhibited by compound 5e at a concentration of 25 mm. Molecular Docking revealed that molecules 5b and 5e consistently showed a large binding affinity for all six target proteins, which was similar to that of the reference molecule, streptomycin. Drug-likeness predictions and the ADME analysis showed that most of the molecules do not violate any of the five Lipinski rule while some have only one or two violations, primarily because of high molecular weight. Novelty: In order to investigate the anti-bacterial impact of piperidine derivatives, a lot of work has been put into their synthesis and evaluation. These results might influence the creation and advancement of anti-microbial medication candidates that are more potent.