Synthesis, characterization, antimicrobial activity, 3D‐QSAR, DFT, and molecular docking of some ciprofloxacin derivatives and their copper(II) complexes

Abstract

Six new derivatives of ciprofloxacin compounds and their copper(II) complexes were synthesized, characterized by spectroscopic methods (ultraviolet–visible [UV–vis], Fourier transform infrared [FTIR], nuclear magnetic resonance [NMR], mass spectrometry [MS], and electron paramagnetic resonance [EPR]), and tested for antibacterial activities against gram‐negative and gram‐positive bacteria. The data showed that ciprofloxacin derivatives act as bidentate ligands and the metal ions coordinate through the pyridone carbonyl and the carboxylate oxygen atoms. Tetragonally distorted octahedral ligand fields were assumed for all complexes based on their spectral studies. Copper(II) complexes of the synthesized ciprofloxacin derivatives revealed higher antibacterial activities against gram‐positive and gram‐negative bacterial species than the parent ciprofloxacin antibiotic. Furthermore, three‐dimensional quantitative structure–activity relationship (3D‐QSAR) models were evaluated by studying 30 antibiotic compounds of the quinolone class. Density function theory (DFT) calculations were applied to evaluate the optimized geometrical structures using the B3LYP method and 6‐311G(d,p) basis set. The 3D‐QSAR study revealed that there are eight optimum parameters that give the best predictive modulation with good reliability (R2 = 0.996, F = 12.004, sigma = 0.426). In silico molecular docking was also performed on the derivatives, and the results revealed the presence of two types of interactions between the Escherichia coli and the derivatives, H‐bonding and Van der Waals interactions, and an effective inhibition at the docked site.

Effects of Magnesium, Calcium, and Aluminum Chelation on Fluoroquinolone Absorption Rate and Bioavailability: A Computational Study

“…An early example from Aristilde et al discloses molecular dynamics (MD) simulations of ciprofloxacin in aqueous solvent and investigates the stability of complexes formed between ciprofloxacin and sodium, potassium, calcium, magnesium, and iron(II) [ 36 ]. Recent examples include DFT computations by Bridle et al modeling pH-dependent complexes of ciprofloxacin and magnesium in aqueous solution [ 37 ], and an experimental and computational study of ciprofloxacin derivatives complexed with copper(II) [ 38 ].…”

Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

“…The results showed that all synthesized hybrids are sensitive against the tested organism, and some of them are exhibited activity higher than the parent drug, ciprofloxacin. The compound 123 was the potent compound in this series and displayed antimicrobial activities against S. aureus, E. coli, and K. pneumonia with inhibition zone, 37, 40, and 11mm respectively higher than ciprofloxacin with inhibition zone, 21mm for all organism using Kirby-Bauer disk diffusion method [148].…”

Recent Studies on the Antimicrobial Activity of Copper Complexes

“…The compound 38a almost inhibit the fungi about 73%. Сiprofloxacin (CF) derivatives HL 39 -HL 44 used for synthesis six copper complexes 39-44 general composition [Cu(L) 2 (H 2 O) x ]•yH 2 O [43]. CF belongs to class II of the second-generation fluoroquino-lone-synthetic antibiotics that are active against both Gram-positive and Gram-negative bacteria.…”

“…(HL 39 ), p-methylphenyl (HL40 ), p-chlorolphenyl (HL41 ), p-nitrophenyl (HL42 ), furan (HL43 ), pyrrol (HL44 ) …”