Synthesis and In Silico Molecular Docking Studies on Substituted Piperic Acid Derivatives as Inhibitors of Bacterial DNA Gyrase

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Author(s): Bhawna Chopra*, Ashwani Kumar Dhingra, Deo Nandan Prasad, Sakshi Bhardwaj, Sonal Dubey.

Journal Name: Current Computer-Aided Drug Design

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Background: A series of piperic acid based N heterocyclic’s derivatives were synthesized and evaluated for antibacterial activity. All these ligands were docked to study the molecular interactions and binding affinities against the protein PDB ID: 5 CDP.

Objective: We have designed and synthesized scaffolds with good antibacterial activity as there is a real need to develop new candidates. The obtained antibacterial activity data have been validated in the terms of ligand-protein interaction and thus proves to build up as good drug candidates.

Methods: All the synthesized compounds have been established by elemental analysis. Antibacterial activity of the compounds were carried out against bacterial strains; three Gram-positive i.e., Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus and three Gram negative bacterial strains i.e., Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi using agar well diffusion method. In silico molecular docking studies were carried out using Glide (grid-based ligand docking) program incorporated in the Schrödinger molecular modeling package by Maestro 11.0.

Results: Compounds BC 28, BC 32 and BC 33 exhibits antibacterial activity along with Gilde docking score of -8.580, -9.753 kcal/mol and -8.813 kcal/mol respectively. Docking studies explained hydrogen bonding, pi-pi and hydrophobic interactions with amino acid residues which explains the binding affinity of most docked ligand with protein

Conclusion: In the present study, substituted piperic acid were synthesized were evaluated as antibacterial compared with standard drug ciprofloxacin and results interprets that having nitrogen as heteroatom in the heterocyclic nucleus found to be more potent than the standard drug ciprofloxacin. On comparing, substitution with electron donating groups generates excellent antibacterial potential against the bacterial strains. It was also proved that having substitution with electron donating groups on meta and para position with triazoline ring system exhibits greater potential while compounds which has a meta- electron donating substituent showed lesser activity with thiazole nucleus. In addition, structure based activities of the prepared analogs was discussed under structure activity relationship (SAR) section.

Keywords: Piperine; piperic acid; antibacterial; triazolines; analogues; docking; 5- CDP

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(E-pub Ahead of Print)
DOI: 10.2174/1573409915666190710092032
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