Pharmacological investigation of formyl and acetyl substituents on piperazine: Docking, ADMET and Molecular Dynamics Simulations

Piperazine-based frameworks are central to the development of many modern therapeutics. Structural modifications on this scaffold influence pharmacological behavior. This study examines the pharmacological influence of formyl and acetyl substituents on the piperazine scaffold. Accordingly, 1-formyl and 1-acetyl piperazine, among the smallest biologically active piperazine derivatives, were selected as model compounds, and their binding potentials and drug-likeness properties were evaluated using molecular docking, in silico ADMET analyses, and molecular dynamics simulations. The interactions of the compounds were investigated with a set of biologically relevant targets (tubulin, E. coli MurB enzyme, serotonin 5-HT3 receptor and human histamine H1 receptor) to explore how formyl and acetyl substituents may affect interaction patterns across different protein environments. The results indicate that formyl and acetyl groups can modulate interaction patterns and pharmacokinetic-related properties of the piperazine scaffold. These findings provide a computational basis for the role of simple functional group modifications on piperazine derivatives.