Design and Synthesis of Thionated Levofloxacin: Insights into a New Generation of Quinolones with Potential Therapeutic and Analytical Applications

Levofloxacin is a widely used fluoroquinolone in several infectious diseases. The structure-activity relationship of levofloxacin has been studied. However, the effect of changing the carbonyl into thiocarbonyl of levofloxacin has not been investigated up to the date of this report. In this work, levofloxacin structure was slightly modified by making a thionated form (compound 3), which was investigated for its antibacterial activity, biocompatibility, and cytotoxicity, as well as spectroscopic properties. The antibacterial susceptibility testing against five different bacteria showed promising minimum inhibitory concentrations (MICs), particularly against B. spizizenii and E. coli, with an MIC value of 1.9 mu M against both bacteria, and 7.8 mu M against P. mirabilis. The molecular docking experiment showed similar binding interactions of both levofloxacin and compound 3 with the active site residues of topoisomerase IV. The biocompatibility and cytotoxicity results revealed that compound 3 was more biocompatible with normal cells and more cytotoxic against cancer cells, compared to levofloxacin. Interestingly, compound 3 also showed an excitation profile with a distinctive absorption peak at lambda(max) 404 nm. Overall, our results suggest that the thionation of quinolones may provide a successful approach toward a new generation with enhanced pharmacokinetic and safety profiles and overall activity as potential antibacterial agents.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
thionated levofloxacin
antibacterial
molecular docking
anticancer
electronic excitation
resistance
Biochemistry & Molecular Biology

Abul-Futouh, H. (author)
Bourghli, L. M. S. (author)
Abu-Sini, M. (author)
Sunoqrot, S. (author)
Ikhmais, B. (author)
Jha, VibhuGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology (author)
Sarayrah, Q. (author)
Abulebdah, D. H. (author)
Ismail, W. H. (author)
Göteborgs universitetInstitutionen för kemi och molekylärbiologi (creator_code:org_t)

In:Current Issues in Molecular Biology: MDPI AG44:10, s. 4626-46381467-30371467-3045

By the author/editor: Ibrahim, A. I. M ...; Abul-Futouh, H.; Bourghli, L. M. ...; Abu-Sini, M.; Sunoqrot, S.; Ikhmais, B.; show more...; Jha, Vibhu; Sarayrah, Q.; Abulebdah, D. H.; Ismail, W. H.; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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