Synthesis, computational studies and <i>in-silico</i> antimicrobial evaluation of novel <i>N</i>-(substituted) sulfonyl carboxamide bearing pyrrolidine-2,5-dione

Novel <i>N</i>-(substituted) sulfonyl carboxamides containing pyrrolidine-2,5-dione or alkyl(aryl)amine moieties, along with some of the intramolecular cyclization derivatives, have been synthesized, designed, and predicted as effective antimicrobial agents. All structures were confirmed by mass spectroscopy,¹H NMR, ¹³C NMR, IR and elemental analysis. Using the DMol³/DFT tool in the Material Studio package, the new carboxamide structures were optimized. The HOMO-LUMO energy gap and the molecular electrostatic potential (MEP) are assessed through density functional calculations. In molecular docking, the studied compounds demonstrated good binding score values (up to −10.0 Kcal/mol) for the active site of tyrosyl-tRNA synthetase protein (PDB ID: 1JIJ) when compared to drugs ciprofloxacin and sulfamethoxazole (−8.5 and −8.0 Kcal/mol, respectively). Notably, compound 2,5-dioxo-<i>N</i>-((4-phenylpiperazin-1-yl)sulfonyl)pyrrolidine-1-carboxamide (<b>1e</b>) demonstrated the highest efficiency, making it a promising antibacterial candidate according to DFT and molecular docking studies. Pharmacological characteristics, including drug similarity and oral bioavailability, have been ascertained using Lipinski’s rule of five. Also, some web tools were used to predict the biological activity of synthesized compounds. The findings indicated potential biological targets and good bacterial activity.