Tag Archives: fluoroquinolone

Preliminary study to obtain some fluoroquinolone-tetracycline hybrids

Ioana-Andreea Lungu1, Lénárd Farczádi2, Zoltán-István Szabó3, Șerban Andrei Gâz4, Octavia-Laura Moldovan1, Aura Rusu5

1. Medicine and Pharmacy Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2. Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3. Pharmaceutical Industry and Management Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
4. Organic Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
5. Pharmaceutical and Therapeutic Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/amma-2024-0034

Objective: This paper aimed to synthesize hybrids of fluoroquinolones with tetracycline class representatives and conduct their preliminary characterization.
Methods: A reaction between tetracycline representatives (doxycycline, tetracycline), formaldehyde (acting as a molecular connector) and fluoroquinolone representatives (ciprofloxacin, moxifloxacin, and norfloxacin) was attempted through a classical reflux synthesis with an electrical heating source (heating mantles) and a microwave-assisted reflux synthesis. One synthesis group also used cupric chloride dihydrate as a catalyst. The samples were analyzed using Differential Scanning Calorimetry, Electrospray Ionization Mass Spectrometry, or High-Performance Liquid Chromatography.
Results: The results indicated the formation of a compound different from the parent components in the case of doxycycline-norfloxacin and possibly tetracycline-norfloxacin hybrids.
Conclusions: Both synthesis methods yielded similar results. The influence of the catalyst did not seem to have been significant. The synthesis method is simple and one-step, using non-toxic solvents. Future studies involving molecular docking and microbiology could be employed to further explore the mechanism of action and the microbiological effects of the hybrids.

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Characterization and Molecular Modelling of Cyclodextrin/Fluoroquinolone Inclusion Complexes

Székely-Szentmiklósi Blanka1, Tőkés B.2

1 Gedeon Richter Romania S.A., Târgu Mureş
2 Department of Physical-Chemistry, University of Medicine and Pharmacy, Târgu Mureş

Background: Cyclodextrins are widely used as complexing agents to increase the solubility of poorly water-soluble drugs, to improve their bioavailability and stability, to reduce or prevent gastrointestinal or ocular irritation, to reduce or eliminate unpleasant smells or tastes and to prevent drug-drug or drug-additive interactions. In recent years, cyclodextrins have been proven to be effective as host compounds in molecular recognition and chiral separation.
Aim: To evaluate the complexation role of cyclodextrins toward fluoroquinolones (FQ) in an attempt to assess their potential as new formulation additives for more efficient fluoroquinolone delivery and as chiral selectors in case of racemic mixture compounds.
Material and methods: Guest-host interactions of three second generation quinolones, ciprofloxacin, ofloxacin and norfloxacin with two parent cyclodextrins, beta-cyclodextrin (b-CD), gamma-cyclodextrin (g-CD) and a beta-cyclodextrin derivative, 2-hydroxypropyl beta-cyclodextrin (HP-b -CD), were tested. Computer aided molecular modelling (ChemBio3D Ultra 12.0) was utilized to predict the preferred orientation of fluoroquinolones in the cyclodextrin cavity and the main structural features responsible for the enhancement of their solubility and photostability. Ciprofloxacin/b-cyclodextrin complex was prepared and the formation of inclusion complex was
demostrated by IR spectroscopy.
Results: Our studies show that the orientation with the piperazinyl group included in the CD cavity is energetically more favorable.
Conclusions: The CDs act as complexing agents with the three FQ derivatives, which enter inside the CD torus, and interact with the hydroxyl groups of CD by Van der Waals, electrostatic forces ang hydrogen bonding. Our results suggest the 1:1 stoichiometry in the complex formation.

Keywords: , , ,
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Study of Cyclodextrin/Fluoroquinolone Inclusion Complexes by Capillary Electrophoresis

Székely-Szentmiklósi Blanka1, Tőkés B2

1 Gedeon Richter Romania S.A., Tîrgu Mureş, Romania
2 Department of Physical-Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania

 

DOI: 10.2478/amma-2013-0026

Introduction: In the present work we evaluated the complexation role of cyclodextrins toward fluoroquinolones in an attempt to assess their potential as new formulation additives for more efficient fluoroquinolone delivery and as selectors in capillary electrophoresis.
Material and method: Guest-host interactions of two second generation quinolones, ciprofloxacin and norfloxacin with four cyclodextrins, beta-cyclodextrin (β-CD), gamma-cyclodextrin (γ-CD) and two beta-cyclodextrin derivatives, 2-hydroxypropyl beta-cyclodextrin (HP-β-CD) and randomly methylated beta-cyclodextrin (RAMEB), were tested by capillary electrophoresis in borate running buffer. Experimental parameters like buffer concentration, pH, organic modifier, voltage and cyclodextrin concentration have been varied for a better resolution.
Results: In capillary zone electrophoresis ciprofloxacin and norfloxacin are migrating together, a difference in their migration times and thus separation occured by the addition of cyclodextrins.
Conclusion: Our results suggest formation of inclusion complexes between fluoroquinolones and cyclodextrins. Differences in their affinity to host molecules resulted in separation of the two fluoroquinolones.

Keywords: , , ,
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