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.