New N -4 piperazinyl derivatives of norfloxacin: design, synthesis, and correlation of calculated physicochemical parameters with antibacterial activity
A group of N−N−N-4 piperazinyl derivatives of norfloxacin was synthesized and
identified by different spectroscopic techniques. The N−N−N-4 piperazinyl
substituent in target compounds 2a-2k, 3a-3c,
and 4a and 4b was designed to have different electronic,
steric, and physicochemical properties. The antibacterial activity of the
newly synthesized compounds was evaluated against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus strains using
norfloxacin as a reference. Results showed that most of the tested compounds
had higher activity against E. coli and K. pneumoniae than norfloxacin, whereas only five
derivatives were more active against P. aeruginosa. On the other hand, all derivatives
were less active than norfloxacin against S. aureus. The biological activity of the
target compounds, expressed in log MIC, is correlated with lipophilicity,
polarizability, and topology parameters. Results showed that none of the
calculated parameters could determine the biological activity. Consequently,
the total volume of the molecule, bulkiness at C-7, electronic factors, and
lipophilicity are important factors that should be considered in the design
of new fluoroquinolones.
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