Synthesis, characterization, molecular docking, and antimicrobial activities of some new sulfur containing norfloxacin analogues

Abstract

The in vitro antimicrobial activity was investigated for two new series of N-4 piperazinyl sulfur containing Ketene S,S-acetals and Ketene N,S-acetals, based norfloxacin analogues against two pathogenic fungi and four pathogenic Gram-positive and Gram-negative bacterial strains. The majority of synthetic compounds exhibit comparable efficacy to norfloxacin against the four tested bacteria. The MIC of the compounds varied from 1.56 to 50 µg/ml. Compounds 8, 9, and 10 exhibited good antifungal activities compared to Griseofulvin. Most of the tested compounds showed promising antibacterial activity. Compounds 4, 9 and 10 showed twice the activity against E. coli (MIC = 3.12 µg/ml), while 6 showed twice the activity against P. aeruginosa (MIC = 6.25 µg/ml), compared to norfloxacin. Similarly, 5 and 9 showed double the activity against k. pneumonia (MIC = 3.12 µg/ml) and 3 showed higher activity against the Gram positive S. aureus. Compounds 1–10 underwent a comprehensive molecular docking investigation with 1HNJ protein from E. coli and showed diverse binding. The binding affinities, expressed as docking scores (S, kcal/mol), exhibited a range from −8.67 (9), −8.47 (10), and −8.45 (8), to −6.85 (7), and −6.47 (3) Kcal/mol. The outcomes of this investigation provide compelling evidence for the inhibitory potential of these compounds against 1HNJ, suggesting a new 1HNJ-targeting agents. Results of Density Functional Theory analysis for 8, 9 and 10 and norfloxacin showed that the calculated HOMO-LUMO energy differences (ΔE), softness, and hardness for compounds 8, 9 and 10 were found to be comparable to that of norfloxacin, emphasizing the significance of charge transfer at the molecular level.