Antimicrobial Evaluation Research Articles

Synthesis and Antimicrobial Evaluation of New 1,2,4-Triazolo[1,5-a]pyrimidine-Based Derivatives as Dual Inhibitors of Bacterial DNA Gyrase and DHFR

Synthesis and Antimicrobial Evaluation of New 1,2,4-Triazolo[1,5-<i>a</i>]pyrimidine-Based Derivatives as Dual Inhibitors of Bacterial DNA Gyrase and DHFR

Machine Learning Approaches for Microorganism Identification, Virulence Assessment, and Antimicrobial Susceptibility Evaluation Using DNA Sequencing Methods: A Systematic Review.

Microbial infections pose a substantial global health challenge, particularly impacting immunocompromised individuals and exacerbating the issue of antimicrobial resistance (AMR). High virulence of pathogens can lead to severe infections and prolonged antimicrobial treatment, increasing the risk of developing resistant strains. Integrating machine-learning (ML) with DNA sequencing technologies offers potential solutions by enhancing microbial identification, virulence assessment, and antimicrobial susceptibility evaluation. This review explores recent advancements in these integrated approaches, addressing current limitations and identifying gaps in the literature. A comprehensive literature search was conducted across databases including PubMed, Scopus, Web of Science, and IEEE Xplore, covering publications from January 2014 to June 2024. Using a detailed Boolean search string, relevant studies focusing on ML applications in microorganism identification, antimicrobial susceptibility testing, and microbial virulence were included. The screening process involved a two-stage review of titles, abstracts, and full texts, with data extraction and critical appraisal performed using the QIAO tool. Data were analyzed through narrative synthesis to identify common themes and innovations. Out of 1,650 initially identified records, 19 studies met the inclusion criteria. These studies primarily focused on AMR, with additional research on microbial virulence and identification. Machine learning algorithms such as Random Forest, Support Vector Machines, and Convolutional Neural Networks, combined with DNA sequencing techniques like Whole Genome Sequencing and Metagenomic Sequencing, demonstrated significant advancements in predictive accuracy and efficiency. High-quality studies achieved impressive performance metrics, including F1-scores up to 0.88 and AUC scores up to 0.96. The integration of ML and DNA sequencing technologies has significantly enhanced microbial analysis, improving the identification of pathogens, assessment of virulence, and evaluation of antimicrobial susceptibility. Despite advancements, challenges such as data quality, high costs, and model interpretability persist. This review highlights the need for continued innovation and provides recommendations for future research to address these limitations and improve disease management and public health strategies. The systematic review is registered with PROSPERO (CRD42024571347).

Potassium Phosphate-Mediated Synthesis of C4-Phosphorylated Quinolines via Cascade Cycloisomerization of Ynones.

A cascade phosphorylation cycloisomerization of readily accessible ynones and diphenylphosphine oxides facilitated by potassium phosphate is described, allowing for the straightforward synthesis of C4-phosphorylated quinoline scaffolds. The formation of a C-P bond and a C-N bond is achieved in a single procedure without the need for pre-assembled quinoline cores prior to phosphorylation. This transformation operates without the requirement for metals or oxidants and exhibits excellent compatibility with various functional groups. Furthermore, antimicrobial activity evaluation demonstrated that the synthesized C4 phosphorylated quinoline derivatives exhibited potent inhibitory activity against Staphylococcus aureus.

Design, Synthesis, Anti-Microbial Evaluation, and Docking Studies of New N-Benzyl-3-Indole Derivatives

Design, Synthesis, Anti-Microbial Evaluation, and Docking Studies of New N-Benzyl-3-Indole Derivatives

Eco-conscious synthesis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives as potent Anti-microbial agent and comparative study of cell viability and cytotoxicity in HEK-293 cell line utilizing Indian gooseberry (Phyllanthus emblica) fruit extract

Antimicrobial resistance (AMR) is a pressing global health challenge that necessitates the search for novel antimicrobial agents and synthetic methodologies. This study investigates the synthesis and antimicrobial efficacy of 25 novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives, catalyzed by Amla (Phyllanthus emblica) fruit juice, which is rich in organic acids and polyphenolic compounds, thus serving as an environmentally sustainable catalyst, in adherence to green chemistry principles. The synthesis is achieved through a one-pot, solvent-free process that yields high quantities of the desired compounds in significantly less time compared to traditional methods. Comprehensive antimicrobial evaluation was conducted against a range of clinically relevant microorganisms, including Chromobacterium violaceum, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Cryptococcus neoformans and Aspergillus niger. Concurrently, cytotoxic assays were performed on HEK-293 cells, to assess safety profiles, revealing that compounds B-1, B-6, B-7, B-14 and B-15 exhibited potent antimicrobial activity while maintaining low cytotoxicity and high cell viability. These findings underscore the therapeutic potential of the synthesized compounds in combatting infectious diseases and addressing the challenges posed by AMR, highlighting the critical importance of dose optimization in therapeutic applications. This study combats contagious diseases, mitigates AMR challenges and contributes significantly to the field of antimicrobial drug discovery, emphasizing the need for sustainable synthetic strategies that align with future pharmaceutical endeavors. Our research not only advances the understanding of these novel compounds but also supports ongoing efforts to develop safe and effective therapies against resistant pathogens.

Development of a porcine model of skin and soft-tissue infection caused by Staphylococcus aureus, including methicillin-resistant strains suitable for testing topical antimicrobial agents.

In view of the ever-increasing representation of Staphylococcus spp. strains resistant to various antibiotics, the development of invivo models for evaluation of novel antimicrobials is of utmost importance. In this article, we describe the development of a fully immunocompetent porcine model of extensive skin and soft tissue damage suitable for testing topical antimicrobial agents that matches the real clinical situation. The model was developed in three consecutive stages with protocols for each stage amended based on the results of the previous one. In the final model, 10 excisions of the skin and underlying soft tissue were created in each pig under general anesthesia, with additional incisions to the fascia performed at the base of the defects and immediately inoculated with Staphylococcus aureus suspension. One pig was not inoculated and used as the negative control. Subsequently, the bandages were changed on Days 4, 8, 11, and 15. At these time points, a filter paper imprint technique (FPIT) was made from each wound for semi-quantitative microbiological evaluation. Tissue samples from the base of the wound together with the adjacent intact tissue of three randomly selected defects of each pig were taken for microbiological, histopathological, and molecular-biological examination. The infection with the inoculated S. aureus strains was sufficient during the whole experiment as confirmed by both FPIT and from tissue samples. The dynamics of the inflammatory markers and clinical signs of infection are also described. A successfully developed porcine model is suitable for invivo testing of novel short-acting topical antimicrobial agents.

Tryptamine‐Derived Schiff Bases: Potent Antimicrobial Agents and Evaluation of Cytotoxicity, ADME and DNA Binding Properties

Inspired by the fact that the introduction of indole pharmacophore in organic scaffolds could enable interesting pharmacological properties, the series of novel tryptamine‐derived Schiff bases was synthetized. Tryptamine was used as a source of indole pattern, as well as an example of biogenic amines which chemical transformations lead to the compounds with prominent biological activities. The obtained results for antimicrobial activity against a range of bacterial and fungal strains and cytotoxic activities have revealed that Schiff base TSB4 combining the tryptamine and p‐nitro aryl patterns in the structure showed better antifungal activity at low concentrations than standard drug Fluconazole, while compound TSB6 with molecular scaffold composed from tryptamine and quinoline moieties showed certain cytotoxic effect on HCT‐116 cell line with a strongly expressed selectivity about healthy fibroblast cells, MRC‐5. For these two selected compounds, additional ADME analysis and DNA interactions were performed. to obtain better insight into their pharmacokinetics and determination of binding mode for DNA molecules. As results suggested, strong binding of examined compounds to CT‐DNA was observed, while the ADME screening showed that selected compounds possess suitable physicochemical properties for oral bioavailability and druglikeness.

Structural and Biological Studies of Bioactive Silver(I) Complexes with Coumarin Acid Derivatives.

Two new Ag(I) complexes with coumaric carboxylic acid derivatives have been synthesized. Structural studies of these noncrystalline complexes have been performed using a methodology that combines laboratory and synchrotron techniques, supported by density functional theory calculations. The arrangement of ligands around the Ag(I) cation has been refined using infrared, extended X-ray absorption fine structure, and X-ray absorption near edge structure spectroscopies. Different coordination modes of carboxylate ligands are observed for the studied compounds. Carboxylate bridges are characteristic for the Ag(I) complex with 4-oxo-4H-1-benzopyran-2-carboxylic acid (1), while a bidentate chelating motif was found for the complex with 2-oxo-2H-1-benzopyran-3-carboxylic acid (2). Additionally, the carbonyl oxygen atom of the coumarin ring coordinates to the silver cation in complex 2, while it is inactive in complex 1. Antimicrobial evaluation has been performed for both compounds. The complexes show activity against selected bacteria as well as Candida yeast. This activity is slightly lower for bacteria and the same or higher for Candida in relation to the reference substances: ciprofloxacin or fluconazole.

Two Step One-Pot Synthesis of 7-Azaindole Linked 1,2,3-Triazole Hybrids: In-Vitro and In-Silico Antimicrobial Evaluation.

Herein, we report design, synthesis and characterization of a new library of 7-azaindole N-ethyl linked 1,2,3-triazoles containing ethylene as a spacer unit, and evaluation of all the synthesized compounds for their antimicrobial properties. Antibacterial potential was checked against two Gram positive (B. subtilis and S. aureus) and two Gram negative (E. coli and P. aeruginosa) bacterial strains while antifungal potential was assayed against two fungal strains (C. albicans and A. niger). All the tested compounds showed satisfactory antibacterial potency in comparison to reference drug ciprofloxacin with MIC values ranging from 0.0108 to 0.0432 μmol/mL. Interestingly, except two, all the target compounds showed better antifungal property as compared to the reference drug fluconazole with MIC values less than 0.0408 μmol/mL. One of the compounds exhibited two-fold better antifungal potential in comparison to fluconazole. Furthermore, in-silico ADMET and DFT studies reported drug likeness behavior and chemical reactivity parameters, respectively. The cytotoxicity results on substrate azide 3 and most potent 1,2,3-triazoles (5 d and 5 l) were found to be non-toxic.

Synthesis, Characterization, and Antimicrobial Evaluation of Thiadiazole Derivatives Derived from 2-Amino-5-Thio-1,3,4-Thiadiazole

This manuscript introduces a series of novel Schiff base and heterocyc-licring compounds, focusing on derivatives of 1,3-oxazepine and thiazo-lidinone.The derivative (2-Hydroxy-N-(5-mercapto-[1,3,4] thiadiazol-2-yl)-2-phenyl-acetamide was created by reacting ethyl mandelate ester[M1] and 2-amino-5-thio-1,3,4-thiadiazole compound to produce new compound [M2] and after that, compound [M2] was reacted with hydrazine hydrate 99% in dry DMF solvent, yielding the compound (N-(5-Hydrazino-[1,3,4]thiadiazol-2-yl)-2-hydroxy-2-phenyl-acetamide [M3]. In contrast , the Schiff base compound [M4] were synthesized by reacting compound [M3] with aromatic heterocyclic aldehyde (furan-2-carbaldehyde) in the presence of glacial acetic acid as a catalyst, and then Schiff base [M4] was reacted with maleic anhydride in dry benzene as a solvent to produce (1,3-Oxazepine) derivative [M5]. Additionally, the thiazolidinone derivative [M6] was synthesized through the reaction of equimolar amounts of (N-[5-(N'-Furan-2-yl-methylene-hydrazino)-[1,3,4]thiadiazol-2-yl]-2-hydroxy-2-phenyl-acetamide [M4] with thioacetic acid compound in chloroform as a solvent. The structural formula of all derivatives was confirmed by FT-IR and (1HNMR, 13CNMR) spectroscopy. The synthesized derivatives [M1-M6] were screened for their evaluated for antibacterial activity against S. aureus, S. epidermidis, E. coli, Klebsiella sp., and the fungus Candida albicans. Dimethyl sulfoxide (DMSO) was used as the solvent. Also, the ampicillin compound was used as the standard drug for comparison.

The impact of a-tomatine on shear bonding strength in different dentin types and on cariogenic microorganisms: an in vitro and in silico study

IntroductionThe objective of this study is to investigate the shear bonding strength of a glycoalkaloid, also a novel matrix metalloproteinase enzyme known as α-tomatine, on two different surfaces of dentin (sound & caries-affected) and its efficacy against cariogenic microorganisms using in vitro and in silico methods.MethodsThe effect of a-tomatine at different concentrations (0.75 / 1 / 1.5 µM) on shear bonding strength in caries-affected and sound dentin was also investigated (n = 10; each per subgroup). The analysis of shear bonding and failure tests was conducted after a 24-hour storage period. Fracture surfaces were examined under a scanning electron microscope. A stock solution 3 mM of a-tomatine was prepared for antimicrobial evaluation. Antimicrobial activities of the agents against Streptococcus mutans ATCC 25175, Lactobacillus casei ATCC 4646, and Candida albicans ATCC 10231 standard strains were investigated by microdilution method. In addition, through the method of molecular docking and dynamic analysis, the affinity of a-tomatine for certain enzymes of these microorganisms was examined.ResultsThe pretreatment agent and dentin type significantly influenced shear bonding strength values (p < 0.05). As the molarity of a-tomatine increased, the bonding value decreased in sound dentin, while the opposite was true in caries-affected dentin. According to molecular docking and dynamic analysis, the highest affinity was observed in L. casei’s signaling protein. Microdilution assays revealed a-tomatine to exhibit fungicidal activity against C. albicans and bacteriostatic effects against S. mutans. No antimicrobial effect was observed on L. casei.Conclusiona-tomatine demonstrates a positive impact by serving as both a pretreatment agent for bonding strength and an inhibitor against certain cariogenic microorganisms.

Synthesis and evaluation of antibacterial and antibiofilm agents based on phenylamino-substituted 1,4-benzoquinones.

Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens.Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p-substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses.Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa, with minimum inhibitory concentrations ranging from 16 to 128μg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128μg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features.Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.

Fabrication of copper ion-substituted hydroxyapatite/Silk fiber/Methylcellulose composite: mechanical, antimicrobial, hemocompatibility, bioactivity and cytocompatibility evaluation

Herein, we reported the preparation of copper substituted hydroxyapatite (Cu-HAP) and fabrication of electrospun composites using Cu-HAP, SF (Silk fiber) and MC (Methylcellulose) by E-Spin method. Characterization techniques such as XRD (phase formation), FTIR (chemical bonds), SEM and EDAX (surface morphology and elemental composition) were carried out. Porosity measurement, swelling and mechanical properties were carried out to investigate the physicochemical properties of the fabricated electrospun composites. The hemocompatibility analysis indicated a hemolysis ratio < 2 %, which confirms the blood compatibility nature of the composite. Antibacterial activity of Copper hydroxyapatite/silk fiber/ Methylcellulose electrospun composite showed estimable activity against E.coli (zone of inhibition: 46 ± 0.94 mm) compared with pure SF/MC electrospun composite (33 ± 1.21). Bioactivity study confirmed the development of bone-like apatite on the surfaces of optimized (SF/MC 30 wt% of Cu-HAP) electrospun composite. Furthermore, MG63 cells were utilised to study the biocompatibility of the enhanced electrospun composite and good cell viability (99.93 ± 0.12 % using 25 μg/mL) was observed from microscopic image and the results showed that 30 wt% of Cu-HAP added polymer composite has outstanding osteoinductivity, biocompatibility, and antibacterial results, making it a very valuable aspirant for use in bone tissue engineering (BTE) applications to repair bone defects.

Antimicrobial evaluation of root canal irrigants of natural sources with and without gamma radiation activation (in vitro study)

ABSTRACT Aims: The present study aimed to evaluate the antibacterial effectiveness of newly formulated root canal irrigants derived from natural sources. In particular, this study investigated how these irrigants’ antimicrobial properties were affected by gamma radiation activation. Materials and Methods: Fifty-three single-rooted extracted human teeth with straight canals were selected, fully prepared, and sterilized. The roots were then infected with Escherichia coli, Enterococcus faecalis, and Candida albicans for 21 days at 37°C. Based on the irrigating solution utilized, the roots were divided into seven groups: Group I: chitosan irrigant, Group II: chitosan irrigant gamma irradiated, Group III: curcumin irrigant, Group IV: curcumin irrigant gamma irradiated, Group V: sodium hypochlorite (NaOCl) 5% irrigant, Group VI: positive control (infected roots without treatment), and Group VII: negative control (uncontaminated roots). After cleaning and shaping, microbiological sampling was performed. The samples were then transferred to sterile centrifuge tubes containing 1 mL of saline to determine the microbial growth. Colony-forming unit counts were employed for assessing the antimicrobial action. Statistical analysis was conducted to compare the percentage reduction in the microbial count from the initial count. Results: Group V and Group IV showed significantly higher values in microbial reduction than Group III and Group I. In addition, the results showed that Group II and Group III have significantly higher values than Group I. Conclusion: Natural irrigating solutions exposed to gamma radiation exhibited promising antimicrobial activity that is comparable to that of NaOCl and may be used as effective antimicrobial agents in endodontic treatment.

Design, Synthesis, and Antimicrobial Evaluation of New Thiopyrimidine-Benzenesulfonamide Compounds.

Bacterial infection poses a serious threat to human life due to the rapidly growing resistance of bacteria to antibacterial drugs, which is a significant public health issue. This study was focused on the design and synthesis of a new series of 25 analogues bearing a 5-cyano-6-oxo-4-substituted phenyl-1,6-dihydropyrimidine scaffold hybridized with different substituted benzenesulfonamides through the thioacetamide linker M1-25. The antimicrobial activity of the new molecules was studied against various Gram-positive, Gram-negative, and fungal strains. All the tested compounds showed promising broad-spectrum antimicrobial efficacy, especially against K. pneumoniae and P. aeruginosa. Furthermore, the most promising compounds, 6M, 19M, 20M, and 25M, were subjected to minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. In addition, the antivirulence activity of the compounds was also examined using multiple biofilm assays. The new compounds promisingly revealed the suppression of microbial biofilm formation in the examined K. pneumoniae and P. aeruginosa microbial isolates. Additionally, in silico ADMET studies were conducted to determine their oral bioavailability, drug-likeness characteristics, and human toxicity risks. It is suggested that new pyrimidine-benzenesulfonamide derivatives may serve as model compounds for the further optimization and development of new antimicrobial and antisepsis candidates.

Pesticide and antimicrobial evaluation of three labdane-type diterpenes, and one flavonoid glycoside, isolated from rhizomes of Hedychium coronarium J. Koenig

Three labdane-type diterpenes, namely coronalactoside I, hedychilactone A, and (E)-labda-8(17),12-dien-15(16)-olide, along with the flavonoid glycoside Isolinariin A, were isolated from Heydichium coronarium. Structural elucidation employed spectroscopic techniques (IR, MS, NMR, and DEPT) and comparison with literature data. Pesticidal and antimicrobial activities were assessed. Isolinariin A exhibited potent nematicidal activity (71.33% mortality) against Meloidogyne incognita, while Coronalactoside I demonstrated strong inhibition of nematode egg hatchability (26.00% at 1 µg/mL). In insecticidal activity against Spodoptera litura, (E)-labda-8(17),12-dien-15(16)-olide displayed significant mortality (93.66% at 100 µg/mL). Molecular docking studies indicated favourable interactions with target proteins, suggesting potential in pest management. These findings propose the application of these compounds to mitigate the ecological impact of synthetic pesticides.

Synthesis, Antimicrobial Evaluation, and Computational Study of Novel Fluorinated Benzofuran Derivatives

Synthesis, Antimicrobial Evaluation, and Computational Study of Novel Fluorinated Benzofuran Derivatives

Green Synthesis of Silver and Copper Nanoparticles Using Parthenium hysterophorus: Antibacterial, Antioxidant, and Anticancer Properties

AbstractNanoparticles (NPs) have gained attention for their unique properties and potential applications, particularly in medicine. This study aim to investigate the green synthesis of silver and copper nanoparticles (NPs) using Parthenium hestephorus extract and evaluate their biological activities. The synthesized NPs were characterized using various analytical techniques, such as UV‐Vis spectroscopy, which confirmed the successful synthesis of silver and copper nanoparticles, with characteristic absorption peaks observed at 450 nm and 580 nm, respectively. Fourier‐transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and energy‐dispersive X‐ray spectroscopy (EDX) were also conducted. In antimicrobial evaluations, the silver and copper nanoparticles exhibited notable inhibitory zones ranging from 12–18 mm against Staphylococcus aureus and 27–30 mm against Escherichia coli bacteria. Furthermore, the nanoparticles’ potential as anticancer agents were tested on HepG2 human cancer cells using the MTT assay. The silver, copper nanoparticles, and control exhibited dose‐dependent cytotoxicity, with IC50 values of 35 μg/mL, 50 μg/ml, and 30 μg/ml, respectively, suggesting their promise in cancer treatment. Antioxidant activity was demonstrated through free radical scavenging assays, with silver and copper nanoparticles showing significant potential, inhibiting free radicals by 80 %, 70 %, and 90 %, respectively. It is concluded that the green synthesis of silver and copper nanoparticles using extract of Parthenium hestephorus presents an efficient and sustainable method for generating NPs with potent antibacterial, anticancer, and antioxidant capabilities.

Ceftazidime with avibactam for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model.

To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of ceftazidime-avibactam in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. The health benefit of ceftazidime-avibactam was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. Patient-level costs and health-related quality of life of ceftazidime-avibactam under various usage scenarios compared with alternative management strategies in the high-value clinical scenarios were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population in quality-adjusted life-years using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for ceftazidime-avibactam. The clinical effectiveness of ceftazidime-avibactam relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. In the base case, ceftazidime-avibactam was associated with a statistically significantly higher susceptibility relative to colistin (odds ratio 7.24, 95% credible interval 2.58 to 20.94). The remainder of the treatments were associated with lower susceptibility than colistin (odds ratio < 1). The results were sensitive to the definition of resistance and the studies included in the analysis. In the base case, patient-level benefit of ceftazidime-avibactam was between 0.08 and 0.16 quality-adjusted life-years, depending on the site of infection and the usage scenario. There was a high degree of uncertainty surrounding the benefits of ceftazidime-avibactam across all subgroups, and the results were sensitive to assumptions in the meta-analysis used to estimate susceptibility. There was substantial uncertainty in the number of infections that are suitable for treatment with ceftazidime-avibactam, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time, and rates of emergence of resistance. The population-level benefit varied substantially across the scenarios, from 531 to 2342 quality-adjusted life-years over 20 years. This work has provided quantitative estimates of the value of ceftazidime-avibactam within its areas of expected usage within the NHS. Given existing evidence, the estimates of the value of ceftazidime-avibactam are highly uncertain. Future evaluations of antimicrobials would benefit from improvements to NHS data linkages, research to support appropriate synthesis of susceptibility studies, and application of routine data and decision modelling to assess enablement value. No registration of this study was undertaken. This award was funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme (NIHR award ref: NIHR135592), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 73. See the NIHR Funding and Awards website for further award information.

Synthesis, Antimicrobial - Cytotoxic Evaluation, and Molecular Docking Studies of Quinolin-2-one Hydrazones Containing Nitrophenyl or Isonicotinoyl/Nicotinoyl Moiety.

By applying the hybrid molecular strategy, in this study, we reported the synthesis of fifteen quinolin-2-one hydrazones containing nitrophenyl or nicotinonyl/isonicotinoyl moiety, followed by in vitro and in silico evaluations of their potential antimicrobial and anticancer activities. In vitro antimicrobial evaluation of the target compounds on seven pathogenic strains, applying the broth microdilution method, revealed that compound 4a demonstrated the most potential antifungal activity against C. albicans (MIC 512 μg mL-1) and C. krusei (MIC 128 μg mL-1). In vitro cytotoxic evaluation of the target compounds on three human cancer cell lines, employing the MTT method, suggested that compound 5c exhibited the most potential cytotoxicities against HepG2 (IC50 10.19 μM), A549 (IC50 20.43 μM), and MDA-MB-231 (IC50 16.82 μM) cells. Additionally, molecular docking studies were performed to investigate the binding characteristics of compounds 4a and 5c with fungal lanosterol 14α-demethylase and human topoisomerase I-II, respectively, thereby contributing to the elucidation of their in vitro antifungal and cytotoxic properties. Furthermore, compounds 4a and 5c, via SwissADME prediction, could exhibit favorable physicochemical and pharmacokinetic properties. In conclusion, this study provides valuable insights into the potential of quinolin-2-one hydrazones as promising candidates for the development of novel antimicrobial and anticancer agents in the future.