Design, synthesis, and molecular docking study of N-(arylsulfonyl)-l-proline-piperazine hybrids tethered with pyrazole/benzofuran moiety as antimicrobial agents

Abstract

In search of novel antimicrobial agents, new series of N-(arylsulfonyl)-l-proline-derived hybrids tethered with pharmacologically attractive cores as 1-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)piperazine and 5-(Piperazin-1-yl)benzofuran-2-carboxamide were synthesized and evaluated for in vitro antimicrobial potential against six different representative human pathogenic strains. Among all, N-acetyl derivative 5e containing phenylpyrazolyl moiety displayed an appreciable inhibitory value (MIC: 107 µg/mL) with noteworthy binding energy (–6.65 kcal/mol) against S. aureus as compared to standard ampicillin (MIC: 250 µg/mL). The N-phenyl-pyrazolyl containing analogue 5b elicited comparable activity against E. coli and P. aeruginosa with MIC values of 104 µg/mL and 121 µg/mL, respectively. Moreover, 5b, 5d, and 6c showed appreciable antioxidant activity (IC₅₀:19.25–20.69 µg/mL) as compared to butylated hydroxytoluene (BHT, IC₅₀:16.47 μg/mL). Molecular docking studies against target tyrosyl-tRNA synthetase (TyrRS) of S. aureus (PDB: 1JIJ) revealed the potential binding mode of the ligands to the appropriate site of targets and their plausible mechanism of in vitro antibacterial activity.

Graphical Abstract

Keywords:

• Antimicrobial activity
• antioxidant activity
• molecular docking
• piperazine
• proline sulfonamides

Acknowledgments

One of the authors Jaydeo T. Kilbile is thankful to the Department of Chemistry, MGM University, Aurangabad for providing essential facilities for research work. We are thankful to the King Saud University, Riyadh, Saudi Arabia for financial support.

Conflict of interest

The authors declare that they have no known competing financial interests or potential conflicts of interest or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

No human/animal studies were carried out in the present work.

Additional information

Funding

We are thankful to the researchers supporting project number (RSPD2024R744), King Saud University, Riyadh, Saudi Arabia for financial support.