Fluorescein-labeled Bacitracin and Daptomycin Conjugates: Synthesis, Fluorescence Imaging and Evaluation

Title:Fluorescein-labeled Bacitracin and Daptomycin Conjugates: Synthesis, Fluorescence Imaging and Evaluation

Volume: 13 Issue: 1

Author(s): Sumbla Sheikh, Alexander Sturzu, Hubert Kalbacher, Thomas Nagele, Christopher Weidenmaier, Marius Horger, Christian Schwentner, Ulrike Ernemann and Stefan Heckl

Affiliation:

Keywords: Daptomycin, bacitracin, fluorescent conjugates, fluorescence imaging, cytotoxicity.

Abstract: Background: Previously, glycopeptides antibiotics such as vancomycin, ramoplanin and an antifungal antibiotic nystatin have been studied for their diagnostic and therapeutic potential.

Objective: To further explore the diagnostic and chemotherapeutic potential of other antibiotics we have now employed daptomycin, a lipopetide antibiotic and bacitracin, a polypeptide antibiotic in uptake and vitality tests on human cell lines.

Method: Fluorescent conjugates of bacitracin and daptomycin were synthesized using fluorescein isothiocynate (FITC) for confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS). The cellular uptake of the synthesized daptomycin and bacitracin conjugates was studied on seven human cell lines, two healthy and five malignant using CLSM and FACS. To examine the cell membrane damage caused by the conjugates FACS experiments were carried out using propidium iodide.

Results: The uptake pattern was different for both antibiotics for all the cell lines. The cytoplasmic uptake of daptomycin conjugate was lower than the bacitracin conjugate, resulting in decreased cell membrane damage.

Conclusion: No preferential uptake into malignant or healthy cells was found for the two different antibiotic conjugates and the uptake patterns were also different between the two antibiotics. However, the lower cytotoxicity and different uptake mechanism makes daptomycin conjugate a prospective candidate for further study as a diagnostic agent for various intracellular infections.

Cite this article as:

Sheikh Sumbla, Sturzu Alexander, Kalbacher Hubert, Nagele Thomas, Weidenmaier Christopher, Horger Marius, Schwentner Christian, Ernemann Ulrike and Heckl Stefan, Fluorescein-labeled Bacitracin and Daptomycin Conjugates: Synthesis, Fluorescence Imaging and Evaluation, Medicinal Chemistry 2017; 13 (1) . https://dx.doi.org/10.2174/1573406412666160330113420

DOI https://dx.doi.org/10.2174/1573406412666160330113420	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638