Search Results (14)

Supramolecular gemifloxacin (GF) sensors have been developed. Supramolecular chemistry is primarily concerned with noncovalent intermolecular and intramolecular interactions, which are far weaker than covalent connections, but they can be exploited to develop sensors with remarkable affinity for a target analyte. In order to determine the dose form of the quinolone antibacterial drug gemifloxacin, the current study’s goal is to adapt three polyvinylchloride (PVC) membrane sensors into an electrochemical technique. Three new potentiometric membrane sensors with cylindric form and responsive to gemifloxacin (GF) were developed. The sensors’ setup is based on the usage of o-nitrophenyl octyl ether (o-NPOE) as a plasticizer in a PVC matrix, β-cyclodextrin (β-CD) (sensor 1), γ-cyclodextrin (γ-CD) (sensor 2), and 4-tert-butylcalix[8]arene (calixarene) (sensor 3) as an ionophore, potassium tetrakis (4-chlorophenyl) borate (KTpClPB) as an ion additive for determination of GF. The developed method was verified according to IUPAC guidelines. The sensors under examination have good selectivity for GF, according to their selectivity coefficients. The constructed sensors demonstrated a significant response towards to GF over a concentration range of 2.4 × 10⁻⁶, 2.7 × 10⁻⁶, and 2.42 × 10⁻⁶ mol L⁻¹ for sensors 1, 2, and 3, respectively. The sensors showed near-Nernstian cationic response for GF at 55 mV, 56 mV, and 60 mV per decade for sensors 1, 2, and 3, respectively. Good recovery and relative standard deviations during the day and between days are displayed by the sensors. They demonstrated good stability, quick response times, long lives, rapid recovery, and precision while also exhibiting good selectivity for GF in various matrices. To determine GF in bulk and dose form, the developed sensors have been successfully deployed. The sensors were also employed as end-point indicators for titrating GF with sodium tetraphenyl borate. Full article

Background: Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological mechanisms, and management of FQNs-associated movement disorders (MDs). Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction between 1988 and 2022. Results: A total of 45 reports containing 51 cases who developed MDs secondary to FQNs were reported. The MDs included 25 myoclonus, 13 dyskinesias, 7 dystonias, 2 cerebellar syndromes, 1 ataxia, 1 tic, and 2 undefined cases. The FQNs reported were ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin, and pefloxacin. The mean and median age were 64.54 (SD: 15.45) and 67 years (range: 25–87 years). The predominant sex was male (54.16%). The mean and median time of MD onset were 6.02 (SD: 10.87) and 3 days (range: 1–68 days). The mean and median recovery time after MD treatment was 5.71 (SD: 9.01) and 3 days (range: 1–56 days). A complete recovery was achieved within one week of drug withdrawal in 80.95% of the patients. Overall, 95.83% of the individuals fully recovered after management. Conclusions: Future cases need to describe the long-term follow-up of the individuals. Additionally, FQN-induced myoclonus should include electrodiagnostic studies. Full article

Moxifloxacin and gemifloxacin are the two newer broad-spectrum 8-methoxy-quinolone derivatives that are used to treat various bacterial infections in cardiac patients. In this research study, we assessed the impact of moxifloxacin and gemifloxacin on the QT intervals of electrocardiograms in normal adult doses and draw a comparison, in a controlled environment, on healthy volunteers. Additionally, the effect of both test drugs on the QRS complex was checked. Sixty healthy volunteers were randomly assigned to two groups via R-software, and each respectively received moxifloxacin and gemifloxacin for five days. The research ethics committee approved the research, and it was registered for clinical trial under NCT 04692623. The participants’ electrocardiograms were obtained before the start of the dose (baseline) and on the fifth day. Significant prolongation of QT interval was noted in moxifloxacin (p < 0.0001) as compared to gemifloxacin treated groups. There were no cases of QTc prolongation over the usual limits (450–470 ms) in the gemifloxacin-treated group, however, QTc prolongations at the rate of 30 and 60 ms from the baseline were noted, interpreted as per the EMEA guidelines. These findings indicate that moxifloxacin caused significant (p < 0.0001) QT interval prolongation (QTIP) as compared to gemifloxacin. In contrast to the previously reported literature, the prominent effect of moxifloxacin on the widening of the QRS-complex was noted with no such effect on QRS-widening in the gemifloxacin-treated group. It is concluded that both drugs have the potential for considerable QT interval prolongation (QTIP) effects, which is one of the risk factors for developing torsade de pointes (TdPs) in cardiac patients. Thus, clinicians should exercise caution when prescribing moxifloxacin and gemifloxacin to cardiac patients and should consider alternate treatment options. Full article

In this paper, novel green HPLC and HPTLC chromatographic methods were developed for the concurrent determination of moxifloxacin, levofloxacin, and gemifloxacin in bulk and pharmaceutical products. The green HPLC method was used on Thermo C18 (4.6 × 250 mm, 5 µm). By mixing ethanol and 20 mM sodium dihydrogen phosphate dihydrate (pH 5) in a ratio of 25:75, v/v, the mobile phase was created using isocratic elution. The flow rate was 1 mLmin⁻¹. The studied antibiotics were separated well within 9.5 min. The green HPTLC method was used on coated HPTLC aluminum sheets with Silica gel 60 F254 using a mobile phase mixture of water: acetone: ammonia (8:1:1, v/v/v). Compact and well-resolved peaks were obtained under chamber-saturation circumstances for the standard fluoroquinolone antibiotics. Both methods were optimized individually, validated by ICH, and assessed using the Green analytical procedure index (GAPI). The methods were applied to pharmaceutical products and compared with the published methods for the determination of each of these antibiotics individually, using Student’s t-test. They can be used by quality-control laboratories in pharmaceutical factories as sensitive eco-friendly methods for the analysis of these drugs and for the detection of cross-contamination during manufacturing processes. Full article

The transcriptional regulator (TcaR) enzyme plays an important role in biofilm formation. Prevention of TcaR-DNA complex formation leads to inhibit the biofilm formation is likely to reveal therapeutic ways for the treatment of bacterial infections. To identify the novel ligands for TcaR and to provide a new idea for drug design, two efficient drug design methods, such as pharmacophore modeling and structure-based drug design, were used for virtual screening of database and lead optimization, respectively. Gemifloxacin (FDA-approved drug) was considered to generate the pharmacophore model for virtual screening of the ZINC database, and five hits, namely ZINC77906236, ZINC09550296, ZINC77906466, ZINC09751390, and ZINC01269201, were identified as novel inhibitors of TcaR with better binding energies. Using structure-based drug design, a set of 7a–7p inhibitors of S. epidermidis were considered, and Mol34 was identified with good binding energy and high fitness score with improved pharmacological properties. The active site residues ARG110, ASN20, HIS42, ASN45, ALA38, VAL63, VAL68, ALA24, VAL43, ILE57, and ARG71 are playing a promising role in inhibition process. In addition, we performed DFT simulations of final hits to understand the electronic properties and their significant role in driving the inhibitor to adopt apposite bioactive conformations in the active site. Conclusively, the newly identified and designed hits from both the methods are promising inhibitors of TcaR, which can hinder biofilm formation. Full article

The binding of fluoroquinolones, the most commonly prescribed antibiotics, with melanin is well explored. However, their binding patterns and exact mechanism of interaction with tyrosinase, a key enzyme in melanogenesis, are not explored yet. Thus, in the present study, seven fluoroquinolone drugs were selected to characterize their interactions with the tyrosinase enzyme: ciprofloxacin, enoxacin sesquihydrate, ofloxacin, levofloxacin, sparfloxacin, moxifloxacin and gemifloxacin. The results confirmed that all the drugs execute excellent enzyme activity, with an inhibition range from IC₅₀ = 28 ± 4 to 50 ± 1.9 μM, outperforming the standard hydroquinone (IC₅₀ = 170 μM). Later, kinetic studies revealed that all the drugs showed irreversible, but mixed-type, tyrosinase inhibition, with a preferentially competitive mode of action. Further, 2D and 3D docked complexes and binding analyses confirmed their significant interactions in the active region of the target enzyme, sufficient for the downstream signaling responsible for the observed tyrosinase inhibition. Thus, this is the first report demonstrating their mechanism of tyrosinase inhibition, critical for melanin-dependent responses, including toxicity. Full article

The convenient synthetic strategy for the one-pot synthesis of silver nanoparticles capped by tartaric acid with a controlled size is reported here. Their characterization is revealed through spectroscopic protocols, such as UV/Vis and FTIR, while SEM, DLS and a Zetasizer revealed the surface morphology, size distribution and surface charge on the nanoparticles. The surface plasmon resonance (SPR) band was observed at 406 nm with 1.07 a.u absorbance, the image for SEM shows that the particles were monodispersed and spherical in shape, while the z-average size distribution of AgNPs/TA in a colloidal solution was found to be 79.20 nm and the surface charge was monitored as −28.2 mV. The antibacterial activities of these capped nanoparticles alone and in synergism with selected fluoroquinolones (ofloxacin, sparfloxacin, ciprofloxacin and gemifloxacin) and macrolides (erythromycin and azithromycin) were assessed on selected Gram-negative as well as Gram-positive organisms by employing the disc diffusion method. Antioxidant activity against the DPPH (1,1-diphenyl-2-picrylhydrazyl) was also evaluated using the standard assay method. The antibacterial activity of the antibiotics has been increased against studied microorganisms, showing the positive synergistic effect of the capped nanoparticles. A potential therapeutic application of AgNPs/TA in combination with antibiotics is determined from the results of the present research. These capped nanoparticles also possess good antioxidant activity and, therefore, can be used in various fields of biomedical sciences. Full article

Four novel ligand-metal complexes were synthesized through the reaction of Fe(III), pleaseCo(II), Zn(II), and Zr(IV) with Schiff base gemifloxacin reacted with ortho-phenylenediamine (GMFX-o-phdn) to investigate their biological activities. Elemental analysis, FT-IR, ¹H NMR, UV-visible, molar conductance, melting points, magnetic susceptibility, and thermal analyses have been carried out for insuring the chelation process. The antimicrobial activity was carried out against Monilinia fructicola, Aspergillus flavus, Penicillium italicum, Botrytis cinerea, Escherichia coli, Bacillus cereus, Pseudomonas fluorescens, and P. aeruginosa. The radical scavenging activity (RSA%) was in vitro evaluated using ABTS method. FT-IR spectra indicated that GMFX-o-phdn chelated with metal ions as a tetradentate through oxygen of carboxylate group and nitrogen of azomethine group. The data of infrared, ¹H NMR, and molar conductivity indicate that GMFX–o-phdn reacted as neutral tetra dentate ligand (N₂O₂) with metal ions through the two oxygen atoms of the carboxylic group (oxygen containing negative charge) and two nitrogen atoms of azomethine group (each nitrogen containing a lone pair of electrons) (the absent of peak corresponding to ν(COOH) at 1715 cm⁻¹, the shift of azomethine group peak from 1633 cm⁻¹ to around 1570 cm⁻¹, the signal at 11 ppm of COOH and the presence of the chloride ions outside the complex sphere). Thermal analyses (TG-DTG/DTA) exhibited that the decaying of the metal complexes exists in three steps with the final residue metal oxide. The obtained data from DTA curves reflect that the degradation processes were exothermic or endothermic. Results showed that some of the studied complexes exhibited promising antifungal activity against most of the tested fungal pathogens, whereas they showed higher antibacterial activity against E. coli and B. cereus and low activity against P. fluorescens and P. aeruginosa. In addition, GMFX-o-phdn and its metal complexes showed strong antioxidant effect. In particular, the parent ligand and Fe(III) complex showed greater antioxidant capacity at low tested concentrations than that of other metal complexes where their IC₅₀ were 169.7 and 164.6 µg/mL, respectively. Full article

Fluoroquinolones (FQs) have been reported to cause dysglycemia in both diabetic and non-diabetic patients. However, diabetic patients are usually on polypharmacy, so we cannot attribute the dysglycemia specifically to FQs. To answer the question as to whether Moxifloxacin and Gemifloxacin influence blood glucose levels and serum insulin levels or otherwise, rabbits were used as experimental animals in an in vivo model followed by a phase I randomized clinical trial in euglycemic healthy volunteers. The effects on the serum insulin and blood glucose levels in the Moxifloxacin and Gemifloxacin treated groups were, respectively, determined on the fifth day in both the in-vivo rabbits model and in the test subjects of the phase I clinical trial. The effects of these drugs were also checked on the histomorphology of the pancreas in the rabbits. The findings of our study suggest that Moxifloxacin and Gemifloxacin significantly (p < 0.05) reduced the blood glucose levels via a subsequent significant shift in the serum insulin levels both in the in vivo animal model and in the test subjects of the phase I clinical trial. No prominent effects on the beta cells histomorphology were noted in this study. Moxifloxacin showed a more significant effect than Gemifloxacin. The insulinotropic effect was comparable to the effect of Glibenclamide. It is concluded that Moxifloxacin and Gemifloxacin have a significant blood glucose lowering effect mediated through insulinotropic action. (Clinical Trials.gov identifier: NCT04692623). Full article

Antimicrobial resistance (AMR) is a neglected issue that poses a serious global threat to public health, causing long-term negative consequences at both humanitarian and economic levels. Herein, we report an unprecedented economic fabrication method of seven potentiometric screen-printed sensors for the ultra-trace determination of gemifloxacin (GEMI) as a model of the fluoroquinolones antibiotics deeply involved in the growing AMR problem. Sensors were constructed by depositing homemade carbon ink on a recycled X-ray sheet, patterned using stencils printed with an office printer in simple, cost-effective steps requiring no sophisticated equipment. Four sensors were modified using carbon quantum dots (CQDs) synthesized from dextrose through a single-step method. Sensors exhibited a linear response in the concentration ranges 10⁻⁵–10⁻² M (sensors 1, 3 and 4), 10⁻⁶–10⁻³ M (sensor 2) and 10⁻⁶–10⁻² M (sensors 5, 6 and 7). LOD allowed tracing of the target drug at a nano-molar level down to 210 nM. GEMI was successfully determined in pharmaceutical formulations and different water samples without any pretreatment steps with satisfactory recovery (96.93–105.28% with SD values < 3). All sensors revealed a long lifetime of up to several months and are considered promising tools for monitoring water quality and efficiency of water treatment measures. Full article

Gemifloxacin is a common oral antibiotic for lower respiratory tract infection worldwide. We noticed an uncommon delayed onset skin rash in patients who received Gemifloxacin. Therefore, we retrospectively reviewed all patients who received Gemifloxacin from 1 January 2011 to 31 May 2016 in a university-affiliated hospital in Taiwan. A total of 1358 patients were enrolled, of whom 36 (2.65%) had skin eruptions. The female patients had a significantly higher odds ratio (OR) 2.24 (95% confidence interval (CI) 1.11–4.53, p = 0.021) of having skin eruptions. A history of asthma was also a significant risk factor (OR 2.04, 95% CI = 1.01–4.14, p = 0.043). Female asthmatic patients had the highest risk of skin eruptions (10/129, 7.2%) with an adjusted OR up to 4.45 (95% CI = 1.81–10.93, p < 0.001) compared to male and non-asthmatic patients. Of note, up to 58.3% (21/36) of the patients experienced a skin rash after they had completed and stopped Gemifloxacin. The median onset time was on the second day (ranging one to five days) after completing treatment. We reported that female asthmatic patients have the highest risk of Gemifloxacin-associated skin eruptions in Asia and that they highlighted a unique delayed onset skin rash. Full article

Three novel mixed ligand metal complexes have been synthesized by the reaction of Zn(II), Sn(II), and Ce(III) with gemifloxacin (GMFX) in the presence of glycine (Gly) (1:1:1 molar ratio). The coordination possibility of the two ligands toward metal ions has been proposed in the light of elemental analysis, molar conductance, spectral infrared (IR), ultraviolet-visible (UV-Vis) and proton-nuclear magnetic resonance (¹H NMR), and magnetic studies. Results suggest that GMFX and Gly interact with the metal ions as bidentate ligands. Electronic and magnetic data proposed the octahedral structure for all complexes under investigation. Antibacterial screening of the compounds was carried out in vitro against two Gram-positive bacteria, Clavibacter michiganensis and Bacillus megaterium, and two Gram-negative bacteria, Escherichia coli and Xanthomonas campestris. Antifungal activity was performed in vitro against Rhizoctonia solani, Sclerotinia sclerotiorum, Aspergillus niger, Botrytis cinerea, and Penicillium digitatum. The ligands and their complexes were also screened for their antioxidant activity. Results showed that some metal complexes showed more biological efficiency than the parent GMFX drug. Full article

Zabofloxacin is a novel fluoroquinolone agent that has potent activity against gram-positive pathogens. In this study, we confirmed that zabofloxacin showed the most potent in vitro and in vivo activities against drug-resistant Streptococcus pneumoniae. Among the fluoroquinolone compounds, zabofloxacin showed the most potent in vitro activity against clinical isolates of penicillin-sensitive S. pneumoniae (minimum inhibitory concentration, MIC₉₀: 0.03 mg/L) and penicillin-resistant S. pneumoniae (MIC₉₀: 0.03 mg/L). Against quinolone-resistant S. pneumoniae, zabofloxacin (MIC₉₀: 1 mg/L) was more active than ciprofloxacin, sparfloxacin, and moxifloxacin; however, its activity was the same as that of gemifloxacin. The in vivo activity of zabofloxacin was most potent among the quinolone compounds tested against the systemic infection and respiratory tract infection models in mice. Full article

A series of novel 7-(3-amino-6,7-dihydro-2-methyl-2H-pyrazolo[4,3-c]pyridin- 5(4H)-yl)fluoroquinolone derivatives were designed, synthesized and characterized by ¹H-NMR, MS and HRMS. These fluoroquinolones were evaluated for their in vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Results reveal that most of the target compounds exhibit good growth inhibitory potency against methicillin-resistant Staphylococcus epidermidis (MRSE) (MIC: 0.25–4 μg/mL) and Streptococcus pneumoniae (MIC: 0.25–1 μg/mL). In addition, compound 8f is 8–128 fold more potent than the reference drugs gemifloxacin (GM), moxifloxacin (MX), ciprofloxacin (CP) and levofloxacin (LV) against methicillin-resistant Staphylococcus aureus 10-05 and Streptococcus hemolyticus 1002 and 2–64 fold more active against methicillin-sensitive Staphylococcus aureus 10-03 and 10-04. Full article