Design,synthesis and biological evaluation of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides as potent Gram-positive antibacterial agents

Twelve 4-benzoyl-1-dichlorobenzoylthiosemicarbazides have been tested as potential antibacterials. All the compounds had MICs between 0.49 and 15.63?µg/ml toward Micrococcus luteus, Bacillus cereus, Bacillus subtilis and Staphylococcus epidermidis indicating, in most cases, equipotent or even more effective action than cefuroxime. In order to clarify if the observed antibacterial effects are universal, further research were undertaken to test inhibitory potency of two most potent compounds 3 and 11 on clinical isolates of Staphylococcus aureus. Compound 11 inhibited the growth of methicillin-sensitive S. aureus (MSSA) at MICs of 1.95–7.81?µg/ml, methicillin-resistant S. aureus (MRSA) at MICs of 0.49–1.95?µg/ml and MDR–MRSA at MIC of 0.98 and 3.90?µg/ml, respectively. Finally, inhibitory efficacy of 3 and 11 on planktonic cells and biofilms formation in clinical isolates of S. aureus and Haemophilus parainfluenzae was tested. The majority of cells in biofilm populations of MSSA and MRSA were eradicated at low level of 3, with MBICs in the range of 7.82–15.63?µg/ml.     

Synthesis and in vitro antimicrobial activity of new 4-phenyl-5-methyl-4H-1,2,4-triazole-3-thione derivatives

This study presents the synthesis, spectral analysis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole (5a–i) and 1,3,4-thiadiazole derivatives (9a, c, g, h). New compounds were obtained by cyclization reaction of acyl thiosemicarbazide derivatives in the presence of alkaline and acidic media. All synthesized compounds were screened for their in vitro antimicrobial activities. Nine of the compounds had potential activity against Gram-positive bacteria (MIC?=?3.91–500 µg/mL). Some compounds showed good activity especially against: Micrococcus luteus ATCC 10240 (MIC?=?3.91?31.25 µg/mL), Bacillus subtilis ATCC 6633 (MIC?=?15.63? 62.5 µg/mL), and Staphylococcus aureus ATCC 25923 (MIC?=?15.63?125 µg/mL).     

Screening of Indonesian peat soil bacteria producing antimicrobial compounds

The development and world-wide spread of multidrug-resistant (MDR) bacteria have a high concern in the medicine, especially the extended-spectrum of beta-lactamase (ESBL) producing Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). There are currently very limited effective antibiotics to treat infections caused by MDR bacteria. Peat-soil is a unique environment in which bacteria have to compete each other to survive, for instance, by producing antimicrobial substances. This study aimed to isolate bacteria from peat soils from South Kalimantan Indonesia, which capable of inhibiting the growth of Gram-positive and Gram-negative bacteria. Isolates from peat soil were grown and identified phenotypically. The cell-free supernatant was obtained from broth culture by centrifugation and was tested by agar well-diffusion technique against non ESBL-producing E. coli ATCC 25922, ESBL-producing E. coli ATCC 35218, methicillin susceptible Staphylococcus aureus (MSSA) ATCC 29,213 and MRSA ATCC 43300. Putative antimicrobial compounds were separated using SDS-PAGE electrophoresis and purified using electroelution method. Antimicrobial properties of the purified compounds were confirmed by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). In total 28 isolated colonies were recovered; three (25PS, 26PS, and 27PS) isolates produced proteins with strong antimicrobial activities against both reference strains. The substance of proteins from three isolates exerted strong antimicrobial activity against ESBL-producing E. coli ATCC 35,218 (MIC = 2,80 µg/mL (25PS), 3,76 µg/mL (26PS), and 2,41 µg/mL (27PS), and MRSA ATCC 43,300 (MIC = 4,20 µg/mL (25PS), 5,65 µg/mL (26PS), and 3,62 µg/mL (27PS), and also had the ability bactericidal properties against the reference strains. There were isolates from Indonesian peat which were potentials sources of new antimicrobials.     

Synergistic effect between dieckol from <Emphasis Type="Italic">Ecklonia stolonifera</Emphasis> and β-lactams against methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

We have been attempting for some time to discover a compound evidencing antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The dieckol isolated from Ecklonia stolonifera has been shown to exhibit antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA. The minimum inhibitory concentrations (MICs) of dieckol were determined in a range of 32 to 64 μg/mL against standard MSSA and MRSA strains. Furthermore, dieckol clearly reversed the high-level ampicillin and penicillin resistance of MRSA. The MICs of ampicillin against two standard strains of MRSA were dramatically reduced from 512 to 0.5 μg/mL in combination with 1/4 MIC of dieckol (16 μg/mL). The fractional inhibitory concentration (FIC) indices of ampicillin and penicillin were measured from 0.066 to 0.266 in combination with 8 or 16 μg/mL of dieckol against all tested MRSA strains, thereby suggesting that dieckol-ampicillin or dieckol-penicillin combinations exert a synergistic effect against MRSA. The results of this study indicate that dieckol, administered in combination with β-lactams, may prove effective in the treatment of MRSA infections. Our finding may also contribute to the development of an alternative phytotherapeutic anti-MRSA agent.     

Antibacterial Effects of Green Tea Polyphenols on Clinical Isolates of Methicillin-Resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

The antibacterial effects of tea polyphenols (TPP) extracted from Korean green tea (Camellia sinensis) against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. Characterization of the minimal inhibitory concentration (MIC) of oxacillin for 30 S. aureus strains isolated from patients treated with oxacillin identified 13 strains with an oxacillin MIC ≥ 4 μg/mL as methicillin-resistant Staphylococcus aureus (MRSA) (range: 8 to 512 μg/mL), while 17 strains were methicillin-susceptible Staphylococcus aureus (MSSA) (range: 0.25–0.5 μg/mL). The MICs of TPP ranged from 50 to 180 μg/mL for both the MSSA and the MRSA strains. The MICs of oxacillin for each of the 13 MRSA strains were reduced between 8- and 128-fold when these strains were coincubated with sub-MIC (≤0.5× MIC) levels of TPP, demonstrating that the combination of TPP plus oxacillin was synergistic for all of the clinical MRSA isolates. Two-dimensional polyacrylamide gel electrophoresis identified 14 extracellular proteins of MRSA-13 down-regulated and 3 proteins up-regulated by exposure to TPP. These studies demonstrate that TPP can differentially stimulate the expression of various proteins in these bacteria and synergize the bactericidal activity of oxacillin for MRSA.     

Synthesis and in vitro antibacterial activity of 7-(3-alkoxyimino-5-amino/methylaminopiperidin-1-yl)fluoroquinolone derivatives

We report herein the design and synthesis of novel 7-(3-alkoxyimino-5-amino/methylaminopiperidin-1-yl)fluoroquinolone derivatives based on the structures of new fluoroquinolones IMB and DZH. The antibacterial activity of these newly synthesized compounds was also evaluated and compared with gemifloxacin, ciprofloxacin, and levofloxacin. Results revealed that all of the target compounds 10-27 have good potency in inhibiting the growth of Staphylococcus aureus including MSSA (MIC: 0.125-8 μg/mL), Staphylococcus epidermidis including MRSE (MIC: 0.25-16 μg/mL), Streptococcus pneumoniae (MIC: 0.125-4 μg/mL), and Escherichia coli (MIC: 0.25-0.5 μg/mL). In particular, some compounds showed useful activity against several fluoroquinolone-resistant strains, and the most active compound 15 was found to be 16-128, 2-32, and 4-8-fold more potent than the three reference drugs against fluoroquinolone-resistant MSSA, MRSA, and MRSE.     

Antibacterial activities of nemonoxacin against clinical isolates of Staphylococcus aureus: an in vitro comparison with three fluoroquinolones

In comparison with ciprofloxacin, levofloxacin and moxifloxacin, antimicrobial activity of nemonoxacin against ciprofloxacin-susceptible/-resistant methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) was determined with the availability to select resistant mutants evaluated. Minimum inhibitory concentrations and mutant prevention concentrations of quinolones were determined by agar dilution method, that concentrated bacterial cells were spread onto Mueller–Hinton agar plates containing antibacterials at different concentrations. Selection index (SI) was calculated. Minimum inhibitory concentration and mutant prevention concentration of nemonoxacin were 0.063 and 0.25 μg/mL for ciprofloxacin-susceptible MSSA and those were 0.5 and 4.0 μg/mL for ciprofloxacin-resistant MSSA, lower than observations of three fluoroquinolones distinctly. SI of nemonoxacin and moxifloxacin were similar, with narrower mutant selective window than levofloxacin and ciprofloxacin. Minimum inhibitory concentration and mutant prevention concentration of nemonoxacin were 0.25 and 2.0 μg/mL for ciprofloxacin-susceptible MRSA, which were 0.5 and 16.0 μg/mL for ciprofloxacin-resistant MRSA. Values were lower than those determined from fluoroquinolones. Nemonoxacin presents good antimicrobial activity against clinical isolates of S. aureus, especially for ciprofloxacin-resistant strains. But stepwise mutant accumulation of ciprofloxacin-resistant MRSA can be hardly inhibited by nemonoxacin with pharmacokinetic parameters considered.     

In vitro activity of the antimicrobial peptide AP7121 against the human methicillin-resistant biofilm producers Staphylococcus aureus and Staphylococcus epidermidis

Abstract

In vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis biofilm producers from blood cultures of patients with prosthetic hip infections was evaluated. The Minimum Inhibitory Concentration (MIC) for AP7121 was determined and the bactericidal activity of AP7121 (MICx1, MICx4) against planktonic cells was studied at 4, 8 and 24?h. The biofilms formed were incubated with AP7121 (MICx1, MICx4) for 1 and 24?h. The anti-adhesion effect of an AP7121-treated inert surface over the highest MIC isolate was studied with scanning electron microscopy (SEM). The bactericidal activity of AP7121 against all the planktonic staphylococcal cells was observed at 4?h at both peptide concentrations. Dose-dependent anti-biofilm activity was detected. AP7121 (MICx4) showed bactericidal activity at 24?h in all isolates. SEM confirmed prevention of biofilm formation. This research showed the in vitro anti-biofilm activity of AP7121 against MRSA and S. epidermidis and the prevention of biofilm formation by them on an abiotic surface.     

Encapsulation in Polymeric Microparticles Improves Daptomycin Activity Against Mature Staphylococci Biofilms—a Thermal and Imaging Study

Eradication of Gram-positive biofilms is a critical aspect in implant-associated infection treatment. Although antibiotic-containing particulate carriers may be a promising strategy for overcoming biofilm tolerance, the assessment of their interaction with biofilms has not been fully explored. In the present work, the antibiofilm activity of daptomycin- and vancomycin-loaded poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (EUD) microparticles against methicillin-resistant Staphylococcus aureus (MRSA) and polysaccharide intercellular adhesin-positive S. epidermidis biofilms was investigated using isothermal microcalorimetry (IMC) and fluorescence in situ hybridization (FISH). The minimal biofilm inhibitory concentrations (MBIC) of MRSA biofilms, as determined by IMC, were 5 and 20 mg/mL for daptomycin- and vancomycin-loaded PMMA microparticles, respectively. S. epidermidis biofilms were less susceptible, with a MBIC of 20 mg/mL for daptomycin-loaded PMMA microparticles. Vancomycin-loaded microparticles were ineffective. Adding EUD to the formulation caused a 4- and 16-fold reduction of the MBIC values of daptomycin-loaded microparticles for S. aureus and S. epidermidis, respectively. FISH corroborated the IMC results and provided additional insights on the antibiofilm effect of these particles. According to microscopic analysis, only daptomycin-loaded PMMA-EUD microparticles were causing a pronounced reduction in biofilm mass for both strains. Taken together, although IMC indicated that a biofilm inhibition was achieved, microscopy showed that the biofilm was not eradicated and still contained FISH-positive, presumably viable bacteria, thus indicating that combining the two techniques is essential to fully assess the effect of microparticles on staphylococcal biofilms.     

Detection of Methicillin-Resistant Staphylococcus aureus Using mecA/nuc Genes and Antibiotic Susceptibility Profile of Malaysian Clinical Isolates

The aim of this study is to compare methicillin-resistant Staphylococcus aureus (MRSA) detection methods and to generate antibiogram profile of S. aureus clinical isolates from two teaching hospitals in Malaysia including three reference isolates from American Type Culture Collection (ATCC). The mecA/nuc gene PCR amplification, spot inoculation test and oxacillin disc diffusion test were applied to compare its MRSA detection abilities. No disagreement between the three methods was observed. From 29 bacterial isolates (including the ATCC strains) tested, 19 isolates were confirmed as S. aureus with 14 isolates exhibiting multidrug-resistance. All isolates are still susceptible to vancomycin as indicated by the E-test result. Current biochemical tests are comparable with the molecular detection method for MRSA used in this study while multidrug-resistance traits are present in both MRSA and MSSA clinical isolates. Presently, mupirocin seems to be the best alternative for vancomycin against multidrug-resistant S. aureus infections in Malaysia. Susceptibility profile of 19 S. aureus isolates acquired from two teaching hospitals and ATCC towards 16 selected antibiotics was analyzed and an antibiogram was generated. Findings also indicated resistance against many of the available antibiotics and thus an urgent need to search for alternative antibiotics.     

Synthesis and anti-staphylococcal activity of novel bacterial topoisomerase inhibitors with a 5-amino-1,3-dioxane linker moiety

Novel bacterial type II topoisomerase inhibitors (NBTIs) constitute a promising new class of antibacterial agents. We report a series of NBTIs with potent anti-staphylococcal activity and diminished hERG inhibition. Dioxane-linked compound 9 demonstrated MICs ≤1?μg/mL against both methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA), accompanied by reduced hERG inhibition as compared to cyclohexane- or piperidine-linked analogs.     

Phytochemical analysis and antibacterial activity towards methicillin-resistant Staphylococcus aureus of leaf extracts from Argania spinosa (L.) Skeels

Argania spinosa (L.) Skeels is an endemic Moroccan species belonging to Sapotaceae family. In this work, lipophilic and aqueous extracts were obtained from leaves and subjected to a chemical profiling by MS and LC-MS/MS. Pentacyclic terpenoids were identified and quantified in the lipophilic fraction, while phenolic compounds (mainly belonging to flavonols and flavan-3-ols) were identified in the aqueous fraction. The antibacterial activities of fractions were evaluated in vitro against both reference Gram-positive and -negative bacterial strains and clinical isolates of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA); in addition, the compounds quantified as main components in each extract were assayed against reference strains. A relevant antibacterial activity was observed against reference MSSA and MRSA strains of S. aureus: for the lipophilic fraction, MIC₅₀ values obtained were 177.8 and 170.6 μg/mL for the former and the latter, respectively, while for the aqueous fraction were 215.5 and 233.3 μg/mL. These inhibitory activities could be mainly ascribed to ursolic and oleanolic acids, among pentacyclic terpenoids, and to quercetin concerning phenolic compounds. A remarkable antibacterial activity was also observed against clinical isolates, thus argan leaves can be considered of interest in the chemotherapy of human infections.     

A novel series of 11-O-carbamoyl-3-O-descladinosyl clarithromycin derivatives bearing 1,2,3-triazole group: Design,synthesis and antibacterial evaluation

A series of novel 11-O-carbamoyl-3-O-descladinosyl clarithromycin derivatives bearing the 1,2,3-triazole group were designed, synthesized, and evaluated for their in vitro antibacterial activity. The antibacterial results indicated that most of the target compounds not only increased their activity against resistant bacterial strains, but also partially retained the activity against sensitive bacterial strains compared with clarithromycin. Among them, 13d had the best antibacterial activity against resistant strains, including Streptococcus pneumoniae B1 expressing the ermB gene (16 µg/mL), Streptococcus pneumoniae AB11 expressing the mefA and ermB genes (16 µg/mL) and Streptococcus pyogenes R1 (16 µg/mL), showing >16, 8 and 16-fold higher activity than that of CAM, respectively. Moreover, 13d and 13g exhibited the best antibacterial activity against sensitive bacterial strains, including Staphylococcus aureus ATCC25923 (4 µg/mL) and Bacillus Subtilis ATCC9372 (1 µg/mL). The MBC results showed that the most promising compounds 13d and 13g exhibited antibacterial activity through bacteriostatic mechanism, while the time-kill kinetic experiment revealed bactericidal kinetics of 13g from microscopic point of view. In vitro antibacterial experiments and molecular docking results further confirmed that it was feasible to our initial design strategy by modifying the C-3 and C-11 positions of clarithromycin to increase the activity against resistant bacteria.     

Design and synthesis of biaryloxazolidinone derivatives containing amide or acrylamide moiety as novel antibacterial agents against Gram-positive bacteria

A series of novel biaryloxazolidinone derivatives containing amide and acrylamide structure were designed, synthesized and evaluated for their antibacterial activity. Most compounds generally exhibited potent antibacterial activity with MIC values of 1 μg/mL against S. aureus, MRSA, MSSA, LREF and VRE pathogens, using linezolid and radezolid as positive controls. Compound 17 exhibited good antibacterial activity with MIC values of 0.5 μg/mL against S. aureus, MRSA, MSSA and VRE and 0.25 μg/mL against LREF. The results indicated that compound 17 might serve as a potential hit-compound for further investigation.     

Anti-pathogenic,antibiofilm, and technological properties of fermented food associated Staphylococcus succinus strain AAS2

Abstract

The present investigation was aimed to determine the anti-pathogenic, antibiofilm, and technological properties of fermented food associated Staphylococcus succinus strain AAS2. The anti-pathogenic attribute of cell-free neutralized supernatant (CFNS) of strain AAS2 was assessed against food-borne and enteric pathogens that revealed promising activity against Staphylococcus aureus and Enterobacter aerogenes with high arbitrary unit of 220.25?±?3.3 and 170.2?±?4.6?AU/mL, respectively. Furthermore, the antibiofilm and time-kill assay of CFNS of strain AAS2 depicted remarkable reduction in biofilm formation of indicator pathogens in a dose-dependent manner. Moreover, time-kill assay data revealed the drastic reduction in the viability (log cfu/mL) of S. aureus and E. aerogenes in the presence of varied minimum inhibitory concentration ranges of CFNS. The distinct technological properties of strain AAS2 were demonstrated using standard methodologies. Reported results estimated moderate level of exopolysaccharide (41.3?±?0.6?mg/L) and lipase production (8.3?±?0.3?mm), followed by remarkable autolytic (30.1?±?1.2–43.1?±?1.3%), catalase (13.82?±?0.3?AU), and nitrate reductase (10.25?±?0.3?mM nitrite/mg dry weight) activities under standard conditions. Most importantly, the strain cleared the specific in vitro safety assessment tests. The described anti-pathogenic and technological traits of strain AAS2 paved the way to utilize it in pharmaceutical as well as food processing industries as starter/adjunct culture.     

3-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones as novel antibacterial scaffolds against methicillin-resistant Staphylococcus aureus

Herein, we report the synthesis and evaluation of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones as antibacterial agents against methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE). Lead compound 38 showed minimum inhibitory concentrations (MICs) of 8 and 4?μg/mL against MRSA and MRSE, respectively. Furthermore, compound 38 displayed a MIC of 8–16?μg/mL against linezolid-resistant MRSA. These molecules, previously underexplored as antibacterial agents, serve as a new scaffold for antimicrobial development.     

Anti‐biofilm activity of ultrashort cinnamic acid peptide derivatives against medical device‐related pathogens

The threat of antimicrobial resistance has placed increasing emphasis on the development of innovative approaches to eradicate multidrug‐resistant pathogens. Biofilm‐forming microorganisms, for example, Staphylococcus epidermidis and Staphylococcus aureus, are responsible for increased incidence of biomaterial infection, extended hospital stays and patient morbidity and mortality. This paper highlights the potential of ultrashort tetra‐peptide conjugated to hydrophobic cinnamic acid derivatives. These peptidomimetic molecules demonstrate selective and highly potent activity against resistant biofilm forms of Gram‐positive medical device‐related pathogens. 3‐(4‐Hydroxyphenyl)propionic)‐Orn‐Orn‐Trp‐Trp‐NH₂ displays particular promise with minimum biofilm eradication concentration (MBEC) values of 125 µg/ml against methicillin sensitive (ATCC 29213) and resistant (ATCC 43300) S. aureus and activity shown against biofilm forms of Escherichia coli (MBEC: 1000 µg/ml). Kill kinetics confirms complete eradication of established 24‐h biofilms at MBEC with 6‐h exposure. Reduced cell cytotoxicity, relative to Gram‐positive pathogens, was proven via tissue culture (HaCaT) and haemolysis assays (equine erythrocytes). Existing in nature as part of the immune response, antimicrobial peptides display great promise for exploitation by the pharmaceutical industry in order to increase the library of available therapeutic molecules. Ultrashort variants are particularly promising for translation as clinical therapeutics as they are more cost‐effective, easier to synthesise and can be tailored to specific functional requirements based on the primary sequence allowing factors such as spectrum of activity to be varied. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Efficacy of novel antibacterial compounds targeting histidine kinase YycG protein

Treating staphylococcal biofilm-associated infections is challenging. Based on the findings that compound 2 targeting the HK domain of Staphylococcus epidermidis YycG has bactericidal and antibiofilm activities against staphylococci, six newly synthesized derivatives were evaluated for their antibacterial activities. The six derivatives of compound 2 inhibited autophosphorylation of recombinant YycG′ and the IC₅₀ values ranged from 24.2 to 71.2 μM. The derivatives displayed bactericidal activity against planktonic S. epidermidis or Staphylococcus aureus strains in the MIC range of 1.5–3.1 μM. All the derivatives had antibiofilm activities against the 6- and 24-h biofilms of S. epidermidis. Compared to the prototype compound 2, they had less cytotoxicity for Vero cells and less hemolytic activity for human erythrocytes. The derivatives showed antibacterial activities against clinical methicillin-resistant staphylococcal isolates. The structural modification of YycG inhibitors will assist the discovery of novel agents to eliminate biofilm infections and multidrug-resistant staphylococcal infections.     

Antibacterial potential of Malaysian ethnomedicinal plants against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA)

This study aimed to evaluate the antibacterial activities of 61 plant extracts from 49 Malaysian ethnomedicinal plants and to investigate the interaction of the active plant extracts in combination with synthetic antibiotics against the MSSA and MRSA strains. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the plant extracts were determined using a microdilution method against MSSA and MRSA strains. The interaction between active plant extracts and the antibiotics was assessed using the checkerboard method. The total fractional inhibitory concentration (∑FIC) indices from the combination were calculated to determine the nature of the interaction. Out of the 61 plant extracts tested against the MSSA strain, 7 plant extracts (̴ 11%) showed MIC values of less than 200 μg/mL, 17 extracts (̴ 28%) showed MIC between 200 and 800 µg/mL and seed extracts of Areca catechu showed MBC values of 400 μg/mL. The seed extract of A. catechu showed MIC and MBC of 400 μg/mL against the MRSA strains while leaf extract of Cocos nucifera showed MIC of 400 μg/mL against MRSA NCTC 12493. When the active plant extracts (MIC ≤ 200 µg/mL for MSSA, and ≤ 400 µg/mL for MRSA) were tested in combination with vancomycin and ciprofloxacin, they showed no interaction against both MSSA and MRSA with ∑FIC between 1.06 and 2.03. These findings provide a preliminary overview of the anti-MSSA and anti-MRSA properties of Malaysian ethnobotanical plants to combat Staphylococcal infections. Further research is needed to establish an antibacterial profile of the tested plant extracts.     

Design and synthesis of biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety as novel antibacterial agents against Gram-positive bacteria

Novel biaryloxazolidinone derivatives containing a rhodanine or thiohydantoin moiety were designed, synthesized and evaluated for their antibacterial activity. The key compounds 7 and 9 were synthesized by the knoevenagel condensation of intermediate aldehyde 5 with rhodanine derivatives 6a?6b. The preliminary study showed that compounds 7, 9 and 10e exhibited potent antibacterial activity with MIC values of 0.125?µg/mL against S. aureus, MRSA, MSSA, LREF and VRE pathogens, using linezolid and radezolid as the positive controls. The most promising compound 10e exhibited potent antibacterial activity against tested clinical isolates of MRSA, MSSA, VRE and LREF with MIC values in the range of 0.125–0.5?µg/mL, and the potency of 10e against clinical isolates of LREF was 64-fold higher than that of linezolid. Moreover, compound 10e was non-cytotoxic with an IC₅₀ value of 91.04?μM against HepG2 cell. Together, compound 10e might serve as a novel antibacterial agent for further investigation.