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

Abstract

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 µM against both bacteria, and 7.8 µM 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 λmax 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.

Enamino Barbiturates as Antiproliferative and Antimicrobial Agents: Studies on Synthesis, Biological Activities, and Molecular Modeling

“…MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) tetrazolium assay was carried out according to the manufactrurer's protocol to detect the metabolic action of living cells using an MTT Cell Proliferation Assay (ATCC®30–1010 K), the absorbance was then recorded at 570 nm using a Synergy™ HTX Multi‐Mode Microplate Reader (BioTek, Winooski, VT, USA). Compounds that caused more than 60 % toxicity in tumor cells and less than 50 % toxicity in normal cell lines were further studied to determine their IC 50 using MTT assay [29] …”

“…Compounds that caused more than 60 % toxicity in tumor cells and less than 50 % toxicity in normal cell lines were further studied to determine their IC 50 using MTT assay. [29] Synthesis Barbituric acid (1) was prepared by the condensation reaction of malonic acid with 1,3-dimethylurea (Figure 2). A white crystal was formed which was further used to the next reactions.…”

Validation of the Absorption-Enhancing Ability of Oligoarginines Grafted onto a Backbone of Hyaluronic Acid through Animal Studies from Rodents to Primates

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Preparation and Characterization of Capsaicin Encapsulated Polymeric Micelles and Studies of Synergism with Nicotinic Acids as Potential Anticancer Nanomedicines

“…The amphiphilicity of this copolymer leads to the formation of micelles in aqueous solutions, where the hydrophobic core contains PPO blocks and the hydrophilic surface layer is comprised of PEO blocks. [ 6 7 8 9 10 11 12 13 14 15 ]…”