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Novel C7 anisidinoquinolones with advantageous antibacterial activity in nanoscale concentrations against standard and resistant bacterial strains.
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- Author(s): ElSheikhi, Somia M.; Darwish, Rula M.; Al-Hiari, Yusuf; Kasabri, Violet; Salih, Mohammed A. F.
- Source:
Pharmacy Practice (1886-3655); Jul-Sep2024, Vol. 22 Issue 3, p1-20, 20p- Subject Terms:
CLINICAL drug trials; IN vitro studies; OXYGENASES; CEPHRADINE; COMBINATION drug therapy; FLUOROQUINOLONES; MICROBIAL sensitivity tests; NUCLEAR magnetic resonance spectroscopy; TETRACYCLINE; RESEARCH funding; DRUG resistance in microorganisms; PATHOLOGIC complete response; AMPICILLIN; BACTERIA; DRUG design; NANOTECHNOLOGY; MASS spectrometry; ERYTHROMYCIN; NEOMYCIN; DRUG development; BACTERIAL diseases; DRUG synergism; BACITRACIN; PHARMACODYNAMICS - Source:
- Additional Information
- Abstract: Background The extensive clinical use of Fluoroquinolones (FQs) led to the development of bacterial resistance against these agents. In this work, new lipophilic FQs were designed, prepared and screened against standard and resistant bacteria. A series of novel 7-substituted anilino-8-nitroFQ acids 3 (a-e), their reduced derivatives 4 (a-e) and their triazolo 5 (a-c) were successfully prepared, identified and characterized using NMR, and MS. FQs 3-5(a-e) were then evaluated for the in vitro antibacterial activity against standard and resistant gram-positive and gram-negative strains using serial dilution method. Combination between the new FQs and different classes of antibiotics were also tested for possible synergistic effect using checkerboard technique. Results The outcomes of the new FQs showed comparable and superior activity against both the standard strains S.aureus and E.coli with remarkable activity against the standard S.aureus strain. The reduced series 4 were the most active group among all derivatives with nanogram concentrations for 4d (60 ng/mL) and 4e (15 ng/mL) against the standard gram positive strain. Our compounds revealed appreciable or comparable MIC mean values to standard against resistant gram-positive strains (MRSA) with no inhibitory activity against gram-negative strains (MDR E.coli). The hydroxyl derivatives 6 have showed the strongest MIC mean values among all compounds. Combination of these compounds with bacitracin, ampicillin and cephalexin showed synergistic effect with fractional inhibitory concentration (FIC) index between 0.185-0.375. While combinations with erythromycin, neomycin and tetracycline showed indifference effect with FIC index 2. Conclusions Evidently increasing number of hydrogen bond acceptor/donor leads to significant increase in activity presented by compounds 4e and 6e. These findings would open the floor for these novel antibacterial agents to be used alone or in combinations with conventional antibiotics for treatment of pathogenic bacteria. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Pharmacy Practice (1886-3655) is the property of Centro de Investigaciones y Publicaciones Farmaceuticas S.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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