Biological evaluation of levofloxacin and its thionated derivatives: antioxidant activity, aldehyde dehydrogenase enzyme inhibition, and cytotoxicity on A549 cell line.

Levofloxacin (LVX) is among the fluoroquinolones antibiotics that has also been studied in vitro and in vivo for its anticancer effects. In this study, we used LVX and novel LVX thionated derivatives; compounds 2 and 3, to evaluate their antioxidant activity, aldehyde dehydrogenase (ALDH) enzymes activity inhibition, and anticancer activity. Combination treatments with doxorubicin (DOX) were investigated as well. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to determine the antioxidant activity. The NADH fluorescence spectrophotometric activity assay was used to determine the ALDH inhibitory effects. Resazurin dye method was applied for cell viability assays. Molecular Operating Environment software was used for the molecular docking experiments. Compared to ascorbic acid, DPPH assay showed that compound 3 had the highest antioxidant activity among the tested compounds with approximately 35% scavenging activity. On ALDH enzymes, compound 3 showed a significant ALDH activity inhibition compared to compound 2 at 200 µM. The IC50 values for the tested compounds were approximately 100 µM on A549 cell line, a non-small cell lung cancer (NSCLC) cell line. However, significant enhancement of cytotoxicity and reduction of IC50 values were observed by combining DOX and synergism was achieved with LVX with a combination index value of 0.4. The molecular docking test showed a minimum binding energy with a good affinity for compound 3 towards ALDH enzymes. Thionated LVX derivatives, may be repurposed for NSCLC therapy in combination with DOX, taking into account the antioxidant activity, ALDH activity inhibition, and the molecular docking results of compound 3.

Development and Comparative Evaluation of Ciprofloxacin Nanoemulsion-Loaded Bigels Prepared Using Different Ratios of Oleogel to Hydrogels.

Nanoemulsions and bigels are biphasic delivery systems that can be used for topical applications. The aim of this study was to incorporate an oil-in-water ciprofloxacin hydrochloride nanoemulsion (CIP.HCl NE) into two types of bigels, Type I (oleogel (OL)-in-hydrogel (WH)) and Type II (WH-in-OL) to enhance drug penetration into skin and treat topical bacterial infections. Bigels were prepared at various ratios of OL and WH (1:1, 1:2, and 1:4). Initially, CIP.HCl NE was prepared and characterized in terms of droplet size, zeta potential, polydispersity index, morphology, and thermodynamic and chemical stability. Then CIP.HCl NE was dispersed into the OL or WH phase of the bigel. The primary physical stability studies showed that Type I bigels were physically stable, showing no phase separation. Whereas Type II bigels were physically unstable, hence excluded from the study. Type I bigels were subjected to microstructural, rheological, in vitro release, antimicrobial, and stability studies. The microscopic images showed a highly structured bigel network with nanoemulsion droplets dispersed within the bigel network. Additionally, bigels exhibited pseudoplastic flow and viscoelastic properties. A complete drug release was achieved after 4-5 h. The in vitro and ex vivo antimicrobial studies revealed that bigels exhibited antimicrobial activity against different bacterial strains. Moreover, stability studies showed that the rheological properties and physical and chemical stability varied based on the bigel composition over three months. Therefore, the physicochemical and rheological properties, drug release rate, and antimicrobial activity of Type I bigels could be modified by altering the OL to WH ratio and the phase in which the nanoemulsion dispersed in.

Isolation and Identification of Coliform Bacteria and Multidrug-Resistant Escherichia coli from Water Intended for Drug Compounding in Community Pharmacies in Jordan.

(1) Background: Water is necessary for the preparation of some medicines found in pharmacies where the local water source does not meet the required purity. This study aimed to investigate the presence of coliform contamination in water used for drug reconstitution in community pharmacies in Jordan. (2) Methods: Two water samples from 50 randomly selected community pharmacies representing all Jordanian governorates were filtered and then cultured in plate count agars to determine total microbial count, and in m-Endo Agar Les and Eosin Methylene Blue (EMB) agar to cultivate Escherichia coli (E. coli). The presence of E. coli was further characterized with gram stains, biochemical tests, and Polymerase chain reaction (PCR). Antibiotic susceptibility of isolated E. coli was tested against a variety of standard antibiotics. (3) Results: Community pharmacies used droppers filled with water from coolers (62%), bottled water (20%), boiled tap water (16%) and tap water (2%). The majority of the sampled water contained coliform bacteria (88%), and E. coli was isolated from 26% of all samples. Statistical analysis showed no significant difference in the percentage of contaminated water samples based on its source location. Nonetheless, the results showed a tendency for higher proportions of contamination in droppers filled from boiled tap water (37.5%; SE: 17.1), followed by water from water coolers (25.8%; SE: 7.9), and then from bottled water (20%; SE: 12.7). All of the isolated E. coli were sensitive to gentamycin, ciprofloxacin and levofloxacin. The susceptibility of the isolates to ceftazidime, doxycycline, tetracycline, azithromycin and amoxicillin/clavulanic acid were 92%, 61%, 46%, 23% and 15%, respectively. (4) Conclusions: This study confirms the widespread presence of multidrug-resistant bacteria in water intended for reconstituting drugs in local pharmacies. These findings expose an alarming situation that needs special attention by the acting pharmacists and competent authorities. Higher levels of personal hygiene in the pharmacies coupled with regular inspection of water quality may reduce the risk of microbial contamination in compounded products, especially multidrug-resistant strains of E. coli and other index microorganisms.

Physicochemical Characteristics and Bioactive Compounds of Different Types of Honey and Their Biological and Therapeutic Properties: A Comprehensive Review.

Honey is considered to be a functional food with health-promoting properties. However, its potential health benefits can be affected by individual composition that varies between honey types. Although studies describing the health benefits of Tualang honey (TH), Kelulut honey (KH), and Sidr honey (SH) are scarce, these honey types showed a comparable therapeutic efficacy to Manuka honey (MH). The purpose of this review is to characterise the physicochemical, biological, and therapeutic properties of TH, KH, and SH. Findings showed that these honeys have antibacterial, antifungal, antiviral, antioxidant, antidiabetic, antiobesity, anticancer, anti-inflammatory and wound-healing properties and effects on the cardiovascular system, nervous system, and respiratory system. The physicochemical characteristics of TH, KH, and SH were compared with MH and discussed, and results showed that they have high-quality contents and excellent biological activity sources. Flavonoids and polyphenols, which act as antioxidants, are two main bioactive molecules present in honey. The activity of honey depends on the type of bee, sources of nectar, and the geographic region where the bees are established. In conclusion, TH, KH, and SH could be considered as natural therapeutic agents for various medicinal purposes compared with MH. Therefore, TH, KH, and SH have a great potential to be developed for modern medicinal use.

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 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.