Synthesis and characterization of Piperine amide analogues: Their In-silico and invitro analysis as potential antibacterial agents

Abstract

Piperine, a natural product obtained from black pepper was structurally modified and a set of 15 piperic amide analogues were synthesized. The molecules were analysed for their ADME properties and binding energy potentials with anti-bacterial target proteins and only the structures that were drug-like were carried forward to synthesis. Then the theoretically potent synthesized analogues were subjected to in-vitro anti-bacterial assay against five bacterial strains, Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, Escherichia faecalis, and Staphylococcus epidermidis. It was noted that the analogues exceeded the activity of piperine at tested concentration. Of all the analogues, trimethyl piperic amide analogue (PA-1) and p-nitro piperic amide analogue (PA-14) has worked exceptionally well against all the strains employed. The mechanism of action of the molecules could be correlated to sulfanamide drugs since the molecular docking results with DHPS protein show correlation with experimental results. The overall ranking of the susceptibility of the tested strains goes as follows, S. epidermidis > S. aureus = A. baumannii > E. faecalis > E. coli.