Targeted Synthesis, In Vitro Antimicrobial Profiling and In Silico Investigation of Furan- and Pyrrole-Linked...

A series of indoline hybrids with amide and sulfonamide functionalities containing furan (6a-k) and pyrrole (13a-k) were synthesized through a multistep process with good yield. The final compounds were purified using reverse-phase flash chromatography and characterized by FTIR, ¹H NMR, ¹³C NMR, LC-MS, and elemental analysis. These compounds were evaluated for their in vitro antibacterial activity against various bacterial strains, including Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Among the compounds tested, compound 6k and 13e exhibited the highest activity, demonstrating potency compared to the standard antibiotic drugs utilized. The antifungal activity of these newly synthesize compounds was also assessed in vitro against Aspergillus niger and Candida albicans, the results emphasized that compounds 6k and 13e displayed the highest activity, compared to the standard antifungal drug nystatin. Furthermore, in silico investigations of compounds 6a-k and 13a-k with E. coli DNA gyrase, using molecular docking and molecular dynamics simulations, revealed exceptional binding affinity of these derivatives to the protein's active site. Additionally, in silico ADMET analysis indicated favorable pharmacokinetic properties with no major toxicity concerns, highlighting their potential as effective antimicrobial agents.