Design, Synthesis and Biological Evaluation of New Piperazin-4-yl-(acetyl-thiazolidine-2,4-dione) Norfloxacin Analogues as Antimicrobial Agents

Abstract

In an effort to improve the antimicrobial activity of norfloxacin, a series of hybrid norfloxacin–thiazolidinedione molecules were synthesized and screened for their direct antimicrobial activity and their anti-biofilm properties. The new hybrids were intended to have a new binding mode to DNA gyrase, that will allow for a more potent antibacterial effect, and for activity against current quinolone-resistant bacterial strains. Moreover, the thiazolidinedione moiety aimed to include additional anti-pathogenicity by preventing biofilm formation. The resulting compounds showed promising direct activity against Gram-negative strains, and anti-biofilm activity against Gram-positive strains. Docking studies and ADMET were also used in order to explain the biological properties and revealed some potential advantages over the parent molecule norfloxacin.

The medicinal perspective of 2,4‐thiazolidinediones based ligands as antimicrobial, antitumor and antidiabetic agents: A review

“…Additionally, in silico and docking studies were performed whose results agreed with the above findings. [ 97 ]…”

“…Additionally, in silico and docking studies were performed whose results agreed with the above findings. [97] F I G U R E 18 Imidazole fused thiazolidinedione conjugates as antimicrobial agents.…”

Norfloxacin Degradation by Persulfate Activated with Cu2O@WO3 Composites: Efficiency, Stability, Mechanism, and Degradation Pathway

“…It has been reported that the bacteriostatic effect of NOR on the cell reproduction suppressor of two enzymesDNA gyrase and DNA topoisomerase IVis vital for DNA replication . To a certain extent, the overuse and even misuse of NOR give rise to norfloxacin-resistant bacterial strains.…”

“…It has been reported that the bacteriostatic effect of NOR on the cell reproduction suppressor of two enzymes�DNA gyrase and DNA topoisomerase IV�is vital for DNA replication. 65 To a certain extent, the overuse and even misuse of NOR give rise to norfloxacin-resistant bacterial strains. To comprehend the various responses of NOR and its intermediate product on different species (i.e., fathead minnow, Daphnia, rats, Tetrahymena pyriformis).…”

The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

“…According to the literature data, nitrogen in piperazine ring can be modified with such heterocyclic moieties as phenylthiazole [13], thiazolidine [14], quinazoline [15], thiadiazole [16,17], pyrimidine [18,19], dithienylethene [20], and 1,2,4-triazole [21]. Azole functionalized hybrids revealed promising levels of antibacterial activity [22], which led us to assume the effectiveness of 1,2,3-triazole moiety utilization for hybrid modification of fluoroquinolones.…”