Search Results (80)

Ruthenocene (Rc) and its derivatives form a structurally versatile class of metallocenes with unique and multifunctional applicability. This review presents a detailed analysis of Rc chemistry including the structural comparison with ferrocene, its redox behavior, and substituent effects. We also discuss its applications in sensing, energy storage, photochemistry, and biomedicine. Rc exhibits unique conformational and adaptive electronic properties based on one and two-electron oxidation processes. Electrochemical investigations of Rc to date indicate that its redox behavior is strongly dependent on the electrolyte system, exhibiting quasi-Nernstian characteristics, the formation of stabilized dimeric species [Rc₂]²⁺, and interconversion among Ru(II), Ru(III), and Ru(IV) oxidation states. Rc-based systems exhibit superior performance as redox mediators and labels in electrochemical sensing systems in terms of electron-transfer kinetics, signal amplification, and surface immobilization. In the field of energy storage, Rc decreases the charging overpotential and increases the cycle life of Li-O₂ batteries. Rc further acts as a photoinitiator via charge-transfer-to-solvent and efficient photoinduced electron transfer in metalloporphyrin and fullerene dyads. In biomedical research, Rc derivatives as well as bioconjugates possess promising anticancer activities, displaying reactive oxygen species generation, topoisomerase inhibition, thioredoxin reductase inhibition, receptor-mediated uptake, and target peptide conjugation. Given its flexible ligand design, electrolyte driven redox behaviors, and antiproliferative properties, Rc exhibits a very adaptive molecular scaffold for next generation electrochemical technologies as well as metallodrug design. Full article

This study reports the synthesis, spectroscopic characterization, and biological evaluation of a novel moxifloxacin hydrazide derivative (MOX-H) and its metal complexes with Co(II), Ni(II), Cu(II), VO(IV), and Gd(III). The ligand was synthesized by hydrazinolysis of moxifloxacin hydrochloride, and the resulting hydrazide was subsequently complexed with the respective metal salts. The interaction between MOX-H and the metal ions yielded the corresponding complexes, formulated as [Co(H₂O)Cl(MOX-H)₂]Cl·2.5H₂O, [Ni(H₂O)Cl(MOX-H)₂]Cl.4.5H₂O, [VO(MOX-H)₂]SO₄.3.5H₂O, [Gd (H₂O)(MOX-H)₂(NO₃)₂]NO₃.2H₂O, and [Cu(MOX-H)₂(H₂O)Cl]Cl·xH₂O (where x = 2, 2.5, 0.5, for products synthesized via template, microwave-assisted, and hydrothermal methods, respectively). The synthesized analogues were characterized by elemental analysis (CHN), FT-IR, UV-visible, and ¹H NMR spectroscopy, and mass spectrometry, as well as thermogravimetric (TG/DTG) and magnetic measurements. FT-IR spectra confirmed coordination through the hydrazide carbonyl and amine groups, while UV–visible and magnetic data indicated predominantly octahedral geometries. The thermal behavior exhibited multistep decomposition with activation parameters supporting exothermic processes. When compared to the free ligand, the metal complexes showed increased antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungus species, particularly for the Co(II) and Cu(II) complexes, which showed the largest inhibition zones. The Cu(II)–MOX-H complex exhibited the lowest MIC values (4.88–9.76 µg/mL) among all tested compounds, confirming its outstanding antibacterial potency and high sensitivity compared to the free ligand and standard drug. Cytotoxicity assays demonstrated selective anticancer activity, with the Cu(II)–MOX-H complex showing the highest potency (IC₅₀ ≈ 2.95 µM against MCF-7 and IC₅₀ ≈ 0.98 µM against HepG-2), while maintaining minimal toxicity toward normal cells. These findings were corroborated by molecular docking investigations, which showed that the MOX-H complexes had substantial binding affinities (−9 to −10 kcal/mol) toward DNA topoisomerase II, consistent with their observed biological effects. Full article

Antimicrobial resistance (AMR) remains a major threat to modern medicine, fueled by the excessive use of antibiotics and the spread of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). In this study, we designed and synthesized a series of 2-aryl-4-aminoquinazoline derivatives bearing an aminoalkylimidazole linker, combining two pharmacophoric motifs associated with antimicrobial activity. Starting from anthranilamide, the compounds were prepared in three straightforward steps, affording good yields and high purity. Their structures were confirmed by FT-IR spectroscopy, ¹H and ¹³C nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Biological evaluation showed that series 5 exhibited strong selectivity toward S. aureus, with compounds 5c and 5d displaying minimum inhibitory concentrations (MICs) between 2.2 and 4.4 µM. No significant activity was observed against other tested strains. Cytotoxicity assays in HepG2 cells revealed moderate to low inhibition. Molecular docking indicated preferential binding to dihydrofolate reductase (DHFR) and relevant interactions with topoisomerase IV, resembling reference inhibitors. ADME analysis predicted favourable absorption, blood–brain barrier permeability, and compliance with Lipinski’s rules. Full article

The microevolutionary pathways and molecular mechanisms by which the important pathogen Vibrio parahaemolyticus acquires resistance in the aquatic environment under continuous selective pressure from quinolone antibiotic residues are still unknown. Here, the study successfully simulated the long-term pressure of antibiotic residues in aquaculture by susceptible V. parahaemolyticus (VPD14) which was isolated from seafood, to a 30-day in vitro induction with sublethal concentrations of levofloxacin, which yielded the mutants (VPD14M). A phenotypic analysis revealed that VPD14M exhibited resistance to ampicillin, levofloxacin and ciprofloxacin, compared to VPD14. These changes were accompanied by adaptations, including a decreased growth rate and an enhanced biofilm formation capacity. Whole-Genome Sequencing identified that the acquired resistance was primarily attributable to key point mutations in three Quinolone Resistance-Determining Regions (QRDRs). Specifically, a G → T substitution at nucleotide position 248 in the gyrA gene, leading to a serine-to-isoleucine substitution at the 83rd amino acid position (Ser83Ile) of the DNA gyrase subunit A; a C → T substitution at position 254 in the parC gene, resulting in a serine-to-phenylalanine substitution at position 85 (Ser85Phe) of the topoisomerase IV subunit A; and a C → T substitution at position 2242 in the gyrB gene, causing a proline-to-serine substitution at position 748 (Pro748Ser) of the DNA gyrase subunit B. Collectively, the study demonstrated that sublethal antibiotic levels rapidly drive quinolone resistance in V. parahaemolyticus, and the specific mutations identified offer critical support for resistance monitoring and seafood safety alerts. Full article

Background/Objectives: The escalating threat of drug-resistant Neisseria gonorrhoeae underscores the urgent need for novel therapeutic agents. Zoliflodacin, a first-in-class spiropyrimidinetrione antibiotic that targets bacterial DNA gyrase and topoisomerase IV, represents a promising candidate for gonorrhea treatment. Methods: From 2020 to 2023, a total of 876 urogenital N. gonorrhoeae isolates were collected from 35 hospitals across Shanghai, China. In vitro susceptibilities to zoliflodacin and six conventional antibiotics (penicillin, tetracycline, ciprofloxacin, azithromycin, ceftriaxone, and spectinomycin) were determined using the agar dilution method. Whole-genome sequencing was conducted to identify sequence types (STs) and amino-acid substitutions in GyrA, GyrB, ParC, ParE, and MtrR. Results: Zoliflodacin exhibited potent in vitro activity, with minimum inhibitory concentrations (MICs) ranging from ≤0.004 to 0.25 mg/L (MIC₅₀ = 0.06 mg/L; MIC₉₀ = 0.125 mg/L), all below the breakpoint (0.5 mg/L). Notably, zoliflodacin maintained high activity against isolates resistant to ceftriaxone, azithromycin, ciprofloxacin, penicillin, and tetracycline. Although all isolates were susceptible to zoliflodacin, elevated MIC values were observed in ST7363 and ST8123 compared with other clones. Genomic analysis identified no substitutions associated with increased zoliflodacin MICs, and most GyrB sequences, the key gene associated with zoliflodacin resistance, remained intact. Conclusions: These findings demonstrate that zoliflodacin possesses robust activity against circulating multidrug-resistant N. gonorrhoeae lineages in Shanghai and support its potential clinical use for the treatment of gonorrhea. Continued genomic and phenotypic surveillance is warranted to preserve the long-term efficacy of this novel agent. Full article

The essential bacterial type II topoisomerases gyrase and topoisomerase IV have been exploited as the therapeutic targets of fluoroquinolone antibacterials for over four decades. Despite their broad utility, the effectiveness of fluoroquinolones has been increasingly undermined by the widespread emergence of target-mediated resistance, highlighting the need for alternative therapeutic strategies. Recent advances have produced two mechanistically distinct classes of gyrase/topoisomerase IV-targeted antibacterials: the triazaacenaphthylenes and the spiropyrimidinetriones. The first-in-class agents gepotidacin and zoliflodacin, respectively, were approved for human use in 2025, representing the first new antibacterial classes targeting these enzymes in decades. This commentary examines the mechanisms of action of these agents, contrasts their interactions with gyrase and topoisomerase IV relative to fluoroquinolones, and considers their potential to address resistance while preserving the long-term clinical viability of therapy directed against the bacterial type II topoisomerases. Full article

The rising resistance of bacterial and fungal strains, particularly in biofilm form, is diminishing the efficacy of available therapies and poses a major threat to human health. This highlights the need for new antimicrobial agents. A review of biological studies has shown that 2,7-naphthyridine derivatives exhibit a wide spectrum of pharmacological properties, including antimicrobial activity, which has contributed to the development of new compounds containing this scaffold. In this work, the obtained compounds were tested to assess their ability to eradicate biofilm formed by selected reference strains of opportunistic pathogens: Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans as well as towards normal microbiota representative, referred to as the Lactobacillus crispatus. The tested 2,7-naphthyridine derivatives showed selective antimicrobial activity, exclusively against S. aureus. 10j demonstrated the highest, among tested compounds, activity on this pathogen (MIC = 8 mg/L), while compound 10f exhibited ~100-fold stronger activity (MIC = 31 mg/L) than the majority of the library compounds. The in vitro assessment on fibroblast cell lines demonstrated low cytotoxicity of both compounds 10f and 10j, which was subsequently confirmed in vivo using the Galleria mellonella larval model, where no signs of systemic toxicity were observed during the 5-day observation period. Due to the structural similarity of the compounds 10f and 10j to typical gyrase/topoisomerase IV inhibitors, molecular dynamics simulations were performed on a ternary complex containing protein, DNAds, and a 1,5-naphthyridine inhibitor (PDB ID: 6Z1A). Molecular dynamics of the gyrase–DNA ternary complex supported stable binding of both hydrazone derivatives, with 10j showing slightly more favorable MM/GBSA energetics driven by electrostatics and halogen bonding, consistent with its ~4-fold lower MIC versus 10f. Taken together, our data highlight compound 10j as a promising microbiota-sparing antibacterial candidate, particularly suitable for selective interventions against S. aureus, for instance in vaginal infections, where targeted eradication of the pathogen without disturbing protective commensals is highly desirable. Full article

The DNA synthesis inhibitor zoliflodacin (ZFD) is expected to be effective against strains resistant to therapeutic agents for Neisseria gonorrhoeae infection. In addition to ZFD, we investigated the susceptibility of N. gonorrhoeae strains to ceftriaxone (CTRX), ciprofloxacin (CPFX), garenoxacin (GRNX), and sitafloxacin (STFX). Minimum inhibitory concentration values for ZFD and four other drugs were determined for 147 strains of N. gonorrhoeae isolated at medical institutions in Hyogo Prefecture, Japan, from 2015 to 2022. Amino acid alterations in gyrA, gyrB, parC, and parE were examined by polymerase chain reaction and sequencing analysis. Sequence type (ST) was determined for epidemiological analysis, and N. gonorrhoeae strains were classified. The non-susceptibility rate was not observed in CTRX. The lowest non-susceptibility rate was observed in ZFD (39.5%) compared to CPFX (80.3%), GRNX (83.7%), and STFX (65.3%) (all p < 0.0001). The most common amino acid alterations in gyrA and parC had non-susceptibility rates exceeding 80% to quinolones except ZFD, suggesting that these alterations may have influenced the resistance trend. STs were different between isolates in 2015 and those in 2020 and later. ZFD showed potent antimicrobial activity against N. gonorrhoeae strains that are highly resistant to quinolones. It may become a new option in the treatment of gonococcal infections. Full article

Background/Objectives: Among Enterobacterales, OXA-48-like-producing Proteus mirabilis strains have been scarcely detected. Herein, we characterized a bla_OXA-48-harbouring P. mirabilis strain recovered from Greece (Pm GR-1), while phylogenomics and comparative genomics analyses with previously published bla_OXA-48 carriers were also assessed. Methods: Characterization of Pm GR-1 was performed by the Vitek^® Compact and Mass Spectrometry systems, antimicrobial susceptibility testing, detection of beta-lactamases, multilocus-sequence typing (MLST), and whole-genome sequencing (WGS). In silico prediction of mobile genetic elements (MGEs), genomic islands (GIs), antimicrobial resistance genes (ARGs) and virulence factors (VFs), and phylogenetic, core-genome SNP and comparative genomics analyses were executed using bioinformatic tools. Results: Pm GR-1 was isolated from a urine sample of an outpatient in a Greek hospital. It exhibited a multidrug-resistant phenotype, being susceptible only to amikacin and ceftazidime/avibactam. It co-carried several beta-lactamase genes on the chromosome (bla_OXA-48, bla_CTX-M-14, bla_TEM-1) and a plasmid (bla_TEM-2) and several other ARGs, but also mutations associated with quinolone resistance in the DNA gyrase and topoisomerase IV subunits. It belonged to the international clone ST135 that has also been detected among OXA-48-producing P. mirabilis strains from Germany and the USA. Pm GR-1 was genetically related to those from Germany, sharing highly similar MGEs, GIs, ARGs and VFs, including the chromosomal bla_OXA-48 genetic structure, the O-antigen locus, the flagella locus, the MR/P fimbriae operon, and the urease gene cluster. Conclusions: To our knowledge, this is the first report from Greece of a bla_OXA-48-possessing P. mirabilis strain. The emergence of bla_OXA-48 among P. mirabilis strains of the international clone ST135 in different geographical regions is worrying. Close monitoring of these strains is required in One Health settings. Full article

Background: Novel norfloxacin derivatives were synthesized, characterized, and screened for their antibacterial activity against Gram-positive strain S. aureus ATCC 6538 and Gram-negative strains; E. coli ATCC 25923, K. pneumoniae ATCC 10031, and P. aeruginosa ATCC 27853 using the agar cup diffusion method. Results: The results revealed that compounds 6–17 exhibited more potent activity towards S. aureus ATCC 6538 with MIC values of 0.21–3.61 µM than norfloxacin with a MIC of 7.83 µM. The most potent compound, 6, showed 37-fold more potency than norfloxacin. More importantly, compound 7 exhibited more potent activity against MRSA than norfloxacin, with MIC values of 0.80 and 1.96 µM, respectively. Meanwhile, compounds 15 and 16 have potent activity towards the Gram-negative strains with MIC values of 0.20–0.79 µM compared with norfloxacin with a MIC of 0.24 µM. Moreover, the potent compounds showed higher activity towards topoisomerase II enzymes, especially against topoisomerase IV, which confirms the docking study with the S. aureus gyrase enzyme active binding site (PDB ID: 2XCT). In addition, cytotoxicity assays of the most potent compounds showed that compounds 6, 7, 15, and 16 have negligible risks of toxic effects when evaluated against the normal cell line WI 38. Conclusions: The docking study of the most potent compounds 6, 7, 15, and 16 on the gyrase enzyme active site (PDB: 2XCT) aligns their antibacterial activity and topoisomerase inhibition. The physicochemical and pharmacokinetic characteristics of the target derivatives were forecasted via SwissADME. Hence, these compounds are considered promising antibacterial candidates that require further optimization. Full article

Background/Objectives: Antimicrobial resistance and oxidative stress are major global health challenges, necessitating the development of novel therapeutic agents. Pyrazole derivatives, known for their diverse pharmacological properties, hold promise in addressing these issues. This study aimed to synthesize new mono- and bis-pyrazole derivatives using an eco-friendly, catalyst-free approach and evaluate their antioxidant, antibacterial, and antifungal activities, supported by in silico ADMET profiling, molecular docking, and Density Functional Theory (DFT) analysis. Methods: The compounds were synthesized via a green condensation reaction and characterized using NMR and mass spectrometry, which was verified by DFT analysis. Biological activities were assessed through DPPH and FRAP antioxidant assays, as well as disk diffusion and MIC methods, against bacterial strains (Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli) and fungal strains (Candida albicans and Aspergillus niger). Computational ADMET profiling evaluated pharmacokinetics and toxicity, while molecular docking assessed interactions with target proteins, including catalase, topoisomerase IV, and CYP51. Results: Theoretical calculations using DFT were in agreement with the experimental results; regarding biological activities, O4 demonstrated the most significant antioxidant activity, with 80.14% DPPH radical scavenging and an IC50 value of 40.91 µg/mL. It exhibited potent antimicrobial activity, surpassing Streptomycin with a 30 mm inhibition zone against Pseudomonas aeruginosa and showing strong efficacy against Staphylococcus aureus and Candida albicans. Computational studies confirmed favorable pharmacokinetic properties, no AMES toxicity, and strong binding affinities. DFT analysis revealed O4’s stability and reactivity, further validating its potential as a therapeutic candidate. Conclusions: This study identified and characterized novel pyrazole derivatives with promising biological and pharmacological properties. O4 emerged as the most potent compound, demonstrating strong antioxidant and antimicrobial activities alongside favorable computational profiles. These findings highlight the potential of the synthetized compounds for therapeutic development and underscore the value of integrating green synthesis with computational techniques in drug discovery. Full article

Background: Irinotecan is a topoisomerase I inhibitor used for the treatment of various cancers, such as gastrointestinal, pancreatic, pulmonary, ovarian, and cervical cancers. Among chemotherapy agents, it represents a rare trigger of drug hypersensitivity reactions, with few cases being reported until today. Methods: We present the case of a patient with metastatic esophageal cancer and a history of irinotecan-induced grade IV (WAO classification) anaphylaxis. An IgE-mediated reaction was confirmed in our case, as evidenced by a positive intradermal skin test result, and we carried out a successful desensitization protocol, given irinotecan’s indispensability in the treatment regimen. Our case underscores the fact that in such situations where the culprit drug is also the only therapeutic option available for such a patient, implementing a desensitization protocol may represent the only viable approach to ensure safe and successful dosing. Results: A comprehensive review of the literature was also conducted to assess previously reported irinotecan-induced hypersensitivity reactions, the utility of skin tests in identifying sensitisation to irinotecan, and the existing desensitization protocols. We found a total of seventeen cases of hypersensitivity reactions to irinotecan in the literature, out of which four provided the skin test results obtained and six performed desensitization protocols for irinotecan. Conclusions: Our literature review highlights that skin testing and desensitization protocols can provide suitable solutions for managing hypersensitivity reactions to irinotecan. Full article

Mycoplasma hyopneumoniae, an important cause of enzootic pneumonia in pigs in many countries, has recently been shown to exhibit reduced susceptibility to several antimicrobial classes. In the present study, a total of 185 pig lung tissue samples were collected from abattoirs in Australia, from which 21 isolates of M. hyopneumoniae were obtained. The antimicrobial resistance profile of the isolates was determined for 12 antimicrobials using minimum inhibitory concentration (MIC) testing, and a subset (n = 14) underwent whole-genome sequence analysis. MIC testing revealed uniformly low values for enrofloxacin (≤1 μg/mL), florfenicol (≤8 μg/mL), lincomycin (≤4 μg/mL), spectinomycin (≤4 μg/mL), tetracycline (≤0.5 μg/mL), tiamulin (≤2 μg/mL), tildipirosin (≤4 μg/mL), tilmicosin (≤16 μg/mL) tulathromycin (≤2 μg/mL), and tylosin (≤2 μg/mL). Higher MICs were observed for erythromycin (MIC range: 16–32 μg/mL), gamithromycin, and tilmicosin (MIC range of both: 32–64 μg/mL). Whole-genome sequencing of the isolates and additional screening using mismatch amplification mutation assay PCR did not identify any known genetic resistance markers within 23S rRNA (macrolides), DNA gyrase A, and topoisomerase IV genes (fluoroquinolones). The WGS data also indicated that the Australian M. hyopneumoniae isolates exhibited limited genetic diversity and formed a distinct monophylectic clade when compared to isolates from other countries. These findings indicate that Australian M. hyopneumoniae likely remains susceptible to the major antimicrobials used to treat enzootic pneumonia in pigs and have evolved in isolation from strains identified in other pig-producing countries. Full article

Dovyalis abyssinica is widely used in Ethiopia for treating various human ailments, yet its pharmacological properties and chemical composition remain largely unexplored. The chromatographic separation of D. abyssinica roots extract afforded five compounds, namely tremulacin (1), cochinchiside A (2), 5-methoxydurmillone (3), catechin-7-O-α-L-rhamnopyranoside (4), and stigmasterol (5), confirmed via IR, NMR, and MS spectral data. This is the first report of these compounds from this plant, except for compounds 1 and 5. The extracts and isolated compounds were tested for antibacterial activity against S. aureus, S. epidermidis, E. faecalis, E. coli, K. pneumoniae, and P. aeruginosa strains. Methanol roots extract exhibited significant antibacterial activity (MIC 0.195 mg/mL) against E. coli and P. aeruginosa. Compounds 1 and 3 showed remarkable antibacterial activity, with compound 1 (MIC 0.625 mg/mL) exhibiting antibacterial activity against S. aureus and S. epidermidis, whereas compound 3 (MIC 0.625 mg/mL) exhibited antibacterial activity against S. epidermidis and K. pneumoniae. Molecular docking analysis revealed better binding energies for compound 1 (−8.0, −9.7, and −8.0 kJ/mol) and compound 3 (−9.0, −8.7, and −8.4 kJ/mol), compared to ciprofloxacin (−8.3, −7.5, and −6.7 kJ/mol), in regard to S. aureus pyruvate kinase, S. epidermidis FtsZ, and K. pneumoniae Topoisomerase IV, respectively. ADME analysis also revealed good antibacterial candidacy of these compounds, provided that in vivo analysis is conducted for further confirmation of the results. Full article

The emergence of antibiotic-resistant Streptococcus pneumoniae necessitates the discovery of novel therapeutic agents. This study investigated the antimicrobial potential of green-synthesized gold nanoparticles (AuNPs) fabricated using Arthrospira platensis extract. Characterization using Fourier transform infrared spectroscopy revealed the presence of functional groups such as ketones, aldehydes, and carboxylic acids in the capping agents, suggesting their role in AuNP stabilization. Transmission electron microscopy demonstrated the formation of rod-shaped AuNPs with a mean diameter of 134.8 nm, as determined by dynamic light scattering, and a zeta potential of −27.2 mV, indicating good colloidal stability. The synthesized AuNPs exhibited potent antibacterial activity against S. pneumoniae, with a minimum inhibitory concentration (MIC) of 12 μg/mL, surpassing the efficacy of the control antibiotic, tigecycline. To elucidate the underlying mechanisms of action, an untargeted metabolomic analysis of the A. platensis extract was performed, identifying 26 potential bioactive compounds belonging to diverse chemical classes. In silico studies focused on molecular docking simulations revealed that compound 22 exhibited a strong binding affinity to S. pneumoniae topoisomerase IV, a critical enzyme for bacterial DNA replication. Molecular dynamics simulations further validated the stability of this protein–ligand complex. These findings collectively highlight the promising antimicrobial potential of A. platensis-derived AuNPs and their constituent compounds, warranting further investigation for the development of novel anti-pneumococcal therapeutics. Full article