Synthesis, Physicochemical Characterization using a Facile Validated HPLC Quantitation Analysis Method of 4-Chloro-phenylcarbamoyl-methyl Ciprofloxacin and Its Biological Investigations.

A novel derivative of ciprofloxacin (Cpx) was synthesized and characterized using various analytical techniques, including FT-IR spectroscopy, UV-Vis spectroscopy, TEM and SEM analysis, 1H NMR, 13C NMR, and HPLC analysis. The newly prepared Cpx derivative (Cpx-Drv) exhibited significantly enhanced antibacterial properties compared to Cpx itself. In particular, Cpx-Drv demonstrated a 51% increase in antibacterial activity against S. aureus and a 30% improvement against B. subtilis. It displayed potent inhibitory effects on topoisomerases II (DNA gyrase and topoisomerase IV) as potential molecular targets, with IC50 values of 6.754 and 1.913 µg/mL, respectively, in contrast to Cpx, which had IC50 values of 2.125 and 0.821 µg/mL, respectively. Docking studies further supported these findings, showing that Cpx-Drv exhibited stronger binding interactions with the gyrase enzyme (PDB ID: 2XCT) compared to the parent Cpx, with binding affinities of -10.3349 and -7.7506 kcal/mole, respectively.

Thiazolidine-2,4-dione-linked ciprofloxacin derivatives with broad-spectrum antibacterial, MRSA and topoisomerase inhibitory activities.

A series of ciprofloxacin/thiazolidine-2,4-dione hybrids 3a-m were prepared and identified by IR, 1HNMR, 13CNMR and elemental analysis. The antibacterial activity results of the designed hybrids revealed a shift of spectrum toward Gram-positive bacteria. They exhibited excellent activity against S. aureus ATCC 6538, with the most potent compounds being 3a, 3e, 3g, 3i, 3k, 3l and 3m possessing MICs of 0.02, 2.03, 0.64, 0.35, 1.04, 0.22 and 0.36 µM, respectively, compared to their parent compound ciprofloxacin (MIC: 5.49 µM). They also showed interesting activity against MRSA AUMC 261 with 3a, 3e and 3l showing MIC values of 5 nM. Reduced activity was observed against Gram-negative bacteria with compound 3l exhibiting a slightly higher activity against K. pneumoniae ATCC10031 with a MIC value of 0. 08 µM. Mechanistically, the incorporation of thiazolidine-2,4-dione ring into ciprofloxacin retained its ability to inhibit DNA synthesis via inhibiting both topoisomerase IV and DNA gyrase of S. aureus. Compounds 3a, 3l and 3m were more potent than ciprofloxacin for topoisomerase IV (IC50 = 0.3-1.9 µM) and gyrase (IC50 = 0.22-0.31 µM) inhibition, which coincide with their antibacterial activity against S. aureus ATCC 6538. Docking against DNA gyrase active site confirmed the ability of the tested compounds to form stable complexes with the enzyme; like that of ciprofloxacin, 3a, 3i, 3k, 3m and 3l reconsidered promising broad-spectrum antibacterial agents targeting topoisomerase IV and gyrase enzymes and have good activity against MRSA.

Synthesis and antimicrobial evaluation of new nitric oxide-donating fluoroquinolone/oxime hybrids.

A new series of nitric oxide-donating fluoroquinolone/oximes was prepared in this study. The nitric oxide release from the prepared compounds was measured using a modified Griess colorimetric method. The antitubercular evaluation of the synthesized compounds indicated that ketone derivatives 2b and 2e and oximes 3b and 3d exhibited somewhat higher activity than their respective parent fluoroquinolones. Mycobacterial DNA cleavage studies and molecular modeling of Mycobacterium tuberculosis DNA gyrase were pursued to explain the observed bioactivity. More important, antibacterial evaluation showed that oximes 3c-e are highly potent against Klebsiella pneumoniae, with minimum inhibitory concentration (MIC) values of 0.06, 0.08, and 0.034 µM, respectively, whereas ketone 2c and oxime 4c are more active against Staphylococcus aureus than ciprofloxacin (MIC values: 0.7, 0.38, and 1.6 µM, respectively). Notably, the antipseudomonal activities of compounds 2a and 4c were much higher than those of their respective parent fluoroquinolones.