Sulfonamide-salicylaldehyde imines active against methicillin- and trimethoprim/sulfonamide-resistant Staphylococci

2021 ◽  
Author(s):  
Martin Krátký ◽  
Klára Konečná ◽  
Jiří Janoušek ◽  
Ondřej Janďourek ◽  
Jana Maixnerová ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bactericidal Effect ◽  
Cross Resistance ◽  
Bacteriostatic Effect ◽  
Gram Positive ◽  
Antimicrobial Drugs ◽  
Active Compounds ◽  
Optimal Activity ◽  
Minimum Inhibitory Concentrations ◽  
Resistant Strains

Background: Increasing resistance has resulted in an urgent need for new antimicrobial drugs. A systematic me-too approach was chosen to modify clinically used sulfonamides to obtain their imines. Methods & results: Twenty-five compounds were synthesized and evaluated for their antibacterial activity. The most active compounds were also investigated against methicillin- and trimethoprim/sulfamethoxazole (SMX)-resistant Gram-positive species. Staphylococci shared the highest susceptibility including resistant strains with minimum inhibitory concentrations from 3.91 μM (≥2.39 μg ml-1). Crucially, the compounds inhibit MRSA and trimethoprim/SMX-resistant Staphylococci without any cross-resistance. Modification of parent sulfonamides turned a bacteriostatic effect into a bactericidal effect. Toxicity for HepG2 and hemolytic properties were also determined. Conclusions: The presence of a dihalogenated salicylidene moiety is required for optimal activity. Based on toxicity, promising derivatives for further investigation were identified.

scholarly journals SCREENING PHYTOCHEMICAL AND ANTI-METHICILLIN RESISTANT (MRSA) ACTIVITY OF 70 % ETHANOLIC EXTRACT FROM THE STEM BARK OF ALBIZIA LEBBECK(L.) BENTH.(FABACEAE)

2018 ◽  
Vol 6 (6) ◽  
pp. 1-6
Author(s):  
Yao KANGA ◽  
CAMARA Djeneb ◽  
KOUASSI Kouadio Aubin ◽  
ZIRIHI Guédé Noël
Keyword(s):  
Antibacterial Activity ◽  
Reference Strain ◽  
Ethanolic Extract ◽  
Stem Bark ◽  
Drug Resistant ◽  
Albizia Lebbeck ◽  
Antimicrobial Drugs ◽  
Methicillin Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

The emergence of multi-drug resistant strains and limitations of present antimicrobial drugs have led to continuous search for natural products as curative agents for Anti-methicillin resistantinfections. The aim of this study was to evaluate antibacterial activity of an ethanolic extract from Albizia lebbeckstem bark against Anti-methicillin resistant. Methods and Results : The methods of dissemination swab on muller-hinton agar and double dilution were used to evaluate the antibacterial activity of 70 % ethanolic extract of stem bark of Albizia lebbeck.All multi-resistant strains of Staphylococcus aureus and the reference strain (ATCC 25923) were sensitive to 70 % ethanolic extract of the stem bark of Albizia lebbeck. The MBCvary from 0,49 mg/mL to 2mg/mL. Also, the phytochemical screening of this extract revealed the presence of  Polyphenols, Gallic tannins, Catechin tanninsand Flavonoids. These findings confirm that an 70 % ethanolic extract from Albizia lebbeck stem bark inhibited growth of Anti-methicillin resistant at low concentration and could be utilised as an alternative Anti-methicillin resistantagent.

Synthesis of Fluorinated Piperazinyl Substituted Quinazolines as Potential Antibacterial Agents

2020 ◽  
Vol 5 (3) ◽  
pp. 227-233
Author(s):  
Amit B. Patel ◽  
Purvesh Patel ◽  
Kajal Patel ◽  
Krupa Prajapati
Keyword(s):  
Antibacterial Activity ◽  
13C Nmr ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Biological Species ◽  
Piperazine Ring ◽  
Minimum Inhibitory Concentrations ◽  
Ft Ir ◽  
Resistant Strains ◽  
Quinazoline Derivatives

In present study, fluorinated piperazine and benzonitrile/nicotinonitrile fused quinazoline derivatives have synthesized, characterized using FT-IR, 1H & 13C NMR, 19F NMR and MS analysis and evaluated as potential antibacterial agents. They were also tested against the multidrug resistant strains. The antibacterial activity results revealed that the majority of synthesized compounds exhibited potential antibacterial with the extraordinary level of minimum inhibitory concentrations comparable to the control drugs. Moreover, the influence of presence or absence of fluoro and trifluoromethyl functional groups on the piperazine ring systems towards different biological species is elaborated. The synthesized compounds were also found non-toxic on the human cervical (HeLa) cells at their minimum inhibitory concentrations.

scholarly journals In VitroAntibacterial Activity of AZD0914, a New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-Positive, Fastidious Gram-Negative, and Atypical Bacteria

2014 ◽  
Vol 59 (1) ◽  
pp. 467-474 ◽  
Author(s):  
Michael D. Huband ◽  
Patricia A. Bradford ◽  
Linda G. Otterson ◽  
Gregory S. Basarab ◽  
Amy C. Kutschke ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Legionella Pneumophila ◽  
Bacterial Species ◽  
Dna Gyrase ◽  
Cross Resistance ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Topoisomerase Inhibitor

ABSTRACTAZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potentin vitroantibacterial activity against key Gram-positive (Staphylococcus aureus,Staphylococcus epidermidis,Streptococcus pneumoniae,Streptococcus pyogenes, andStreptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzaeandNeisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance inS. aureus, and if mutants were obtained, the mutations mapped togyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration andin vitrotime-kill studies. Inin vitrocheckerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potentin vitroantibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.

Combination Therapy for Bacterial Pathogens: Naturally Derived Antimicrobial Drugs Augmented with Ulva lactuca Extract

2021 ◽  
Vol 21 ◽  
Author(s):  
Nilushi Indika Bamunuarachchi ◽  
Fazlurrahman Khan ◽  
Young-Mog Kim
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Bacterial Pathogens ◽  
Dilution Method ◽  
Gram Positive ◽  
Antimicrobial Drugs ◽  
Gram Negative ◽  
Hexane Extracts ◽  
Conventional Antibiotics

Background: With the growing incidence of microbial pathogenesis, several alternative strategies have been developed. The number of treatments using naturally (e.g., plants, algae, fungi, bacteria, and animals) derived compounds has increased. Importantly, marine-derived products have become a promising and effective approach to combat the antibiotic resistance properties developed by bacterial pathogens. Furthermore, augmenting the sub-inhibitory concentration of the naturally-derived antimicrobial compounds (e.g., hydroxycinnamic acids, terpenes, marine-derived polysaccharides, phenolic compounds) into the naturally derived extracts as a combination therapy to treat the bacterial infection has not been well studied. Objective: The present study was aimed to prepare green algae Ulva lactuca extract and evaluate its antibacterial activity towards Gram-positive and Gram-negative human pathogenic bacteria. Also, revitalize the antibacterial efficiency of the naturally-derived antimicrobial drugs and conventional antibiotics by augmenting their sub-MIC to the U. lactuca extracts. Methods: Extraction was done using a different organic solvent, and its antibacterial activity was tested towards Gram-positive and Gram-negative pathogens. The minimum inhibitory concentration (MIC) of U. lactuca extracts has been determined towards pathogenic bacteria using the micro broth dilution method. The viable cell counting method was used to determine the minimum bactericidal concentration (MBC). The fractional inhibitory concentration (FIC) assay was utilized to examine the combinatorial impact of sub-MIC of two antibacterial drugs using the micro broth dilution method. The chemical components of the extract were analyzed by GC-MS analysis. Results: Among all the extracts, n-hexane extract was found to show effective antibacterial activity towards tested pathogens with the lowest MIC and MBC value. Furthermore, the n-hexane extracts have also been used to enhance the efficacy of the naturally-derived (derived from plants and marine organisms) compounds and conventional antibiotics at their sub-inhibitory concentrations. Most of the tested antibiotics and natural drugs at their sub-MIC were found to exhibit synergistic and additive antibacterial activity towards the tested bacterial pathogens. Conclusions: The augmenting of U. lactuca n-hexane extracts resulted in synergistic and additive bactericidal effects on Gram-positive and Gram-negative human pathogenic bacteria. The present study shows a new alternative strategy to revitalize the antimicrobial activity of naturally derived compounds for treating human bacterial pathogens.

scholarly journals Lefamulin: novel pleuromutilin drug for community acquired bacterial pneumonia

2019 ◽  
Vol 8 (12) ◽  
pp. 2783
Author(s):  
A. P. Dubey ◽  
Sachin Maggo ◽  
Awanish Karan ◽  
N. K. Singh ◽  
Sreya Bhaskaran
Keyword(s):  
Legionella Pneumophila ◽  
Bacterial Pneumonia ◽  
Similar Efficacy ◽  
Cross Resistance ◽  
Global Public Health ◽  
Gram Positive ◽  
Antimicrobial Drugs ◽  
Mycoplasma Pneumonia ◽  
Us Fda ◽  
Enzyme Elevation

The advent and spread of antimicrobial resistance has led to a global public health emergency necessitating development of new antimicrobial drugs. Community acquired bacterial pneumonia (CABP) contributes a major portion of societal burden with increasing morbidity due to evolution of drug resistant strains. Lefamulin is a novel pleuromutilin antibiotic with unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50s bacterial ribosome. The drug displays activity against Gram positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumonia, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded Gram-positive spectrum including Staphylococcus aureus (i.e., methicillin-resistant, vancomycin-intermediate, and heterogeneous strains). Lefamulin is available in both intravenous (IV) and per oral (PO) formulation, exhibits high nonlinear plasma protein binding with low unbound concentrations, higher concentrations in lung epithelial lining fluid (ELF) than in plasma, and a half-life of approximately 10 hour. The recommended IV dose is 150 mg twice daily over 1 hour or a PO dose of 600 mg twice daily. Most common adverse drug reactions injection site reactions, hepatic enzyme elevation, nausea, diarrhoea, hypokalemia, insomnia, and headache. Clinical trials for lefamulin have been positive and Phase 3 data suggest similar efficacy when compared to moxifloxacin with or without linezolid in CABP. Also, the documented resistance and cross-resistance with other Gram-positive antibacterials remains low. With Nabrivia Pharmaceuticals having already received US FDA approval in August 2019, lefamulin may soon be a new addition to the mounting armoury of drugs against CABP. 

scholarly journals Use of Linezolid in the treatment of surgical infectious complications under antibiotic resistance

2021 ◽  
Vol 3 (2) ◽  
pp. 34-39
Author(s):  
O A Nazarchuk ◽  
V L Vitkovskiy ◽  
Yu M Babina
Keyword(s):  
Pharmacokinetic Profile ◽  
Infectious Complications ◽  
Community Acquired Pneumonia ◽  
Cross Resistance ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
New Class ◽  
Resistant Strains ◽  
Unique Mechanism ◽  
Antibacterial Spectrum

Linezolid – a first representative of the new class of synthetic antibiotics oxazolidones. Its antibacterial spectrum includes Gram-positive microorganisms, including multi-resistant strains. Its unique mechanism of action conditions absence of cross-resistance with other antibiotics. This drug is presented in peroral and parenteral forms. Unlike vancomycin, it has optimal pharmacokinetic profile. Linezolid was approved by Food and Drug Administration (FDA) in 2000 for the treatment of the following diseases: hospital- and community-acquired pneumonia, skin and soft tissue infections with or without complications caused by Gram-positive bacteria, vancomycin-resistant enterococci and pneumococcal meningitis, caused by penicillin-resistant Streptococcus pneumoniae.

scholarly journals Activity of a New Oral Streptogramin, XRP2868, against Gram-Positive Cocci Harboring Various Mechanisms of Resistance to Streptogramins

2006 ◽  
Vol 50 (1) ◽  
pp. 237-242 ◽  
Author(s):  
Michel Dupuis ◽  
Roland Leclercq
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bactericidal Effect ◽  
The Other ◽  
Mechanisms Of Resistance ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Strong Activity ◽  
Factor B ◽  
Gram Positive Cocci

ABSTRACT The antibacterial activity of XRP2868, a new oral streptogramin composed of a combination of RPR132552 (streptogramin A) and RPR202868 (streptogramin B), was evaluated against a collection of clinical gram-positive isolates with characterized phenotypes and genotypes of streptogramin resistance. The effects of genes for resistance to streptogramin A or B on the activity of XRP2868 and its components were also tested by cloning these genes individually or in various combinations in gram-positive recipient strains susceptible to quinupristin-dalfopristin. The species tested included Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, and other species of streptococci. XRP2868 was generally fourfold more potent than quinupristin-dalfopristin against S. aureus, E. faecium, and streptococci and had activity against E. faecalis (MICs = 0.25 to 1 μg/ml). XRP2868 appeared to be affected by the same mechanisms of resistance as those to quinupristin-dalfopristin. Nevertheless, the strong activity of factor A of the oral streptogramin enabled the combination to be very potent against streptogramin-susceptible staphylococci, streptococci, and E. faecium (MICs = 0.03 to 0.25 μg/ml) and to retain low MICs against the strains harboring a mechanism of resistance to factor A or factor B of the streptogramin. However, the combination of mechanisms of resistance to factors A and B caused an increase in the MICs of XRP2868, which reached 1 to 4 μg/ml. As with the other streptogramins, there was a reduction in the bactericidal effect of XRPR2868 when the staphylococcal strains acquired a constitutively expressed erm gene.

scholarly journals Antimicrobial Diterpenes from Azorella Species against Gram-Positive Bacteria

2015 ◽  
Vol 10 (11) ◽  
pp. 1934578X1501001 ◽  
Author(s):  
Viviana Donoso ◽  
Mitchell Bacho ◽  
Solange Núñez ◽  
Juana Rovirosa ◽  
Aurelio San-Martín ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Mycobacterium Smegmatis ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Resistant Strains ◽  
Andean Plants

The present study was aimed at evaluating the antibacterial activity of mulinane and azorellane diterpenes isolated from the Andean plants Azorella compacta and A. trifoliolata and semisynthetic derivatives against reference and multidrug-resistant strains. The results revealed that the semisynthetic compound 7-acetoxy-mulin-9,12-diene (5) exhibited antibacterial activity against reference and multidrug-resistant strains of Staphylococcus aureus and moderate antimycobacterial activity against Mycobacterium smegmatis ATCC 14468.

6-Aminopenicillanic acid IV. Antibacterial activity

1961 ◽  
Vol 154 (957) ◽  
pp. 509-513 ◽  
Keyword(s):  
Cell Wall ◽  
Antibacterial Activity ◽  
Cell Wall Formation ◽  
Gram Positive ◽  
Gram Negative ◽  
Wall Formation ◽  
Minimum Inhibitory Concentrations ◽  
Gram Positive Cocci

6-Aminopenicillanic acid shows a similar order of activity against the Gram-positive cocci as against the Gram-negative bacilli. Compared with benzylpenicillin, the activity against the Gram-positive cocci is very low but against the Gram-negative bacilli, 6-aminopenicillanic acid shows a similar order of activity to benzylpenicillin. 6-Aminopenicillanic acid is bacteri­cidal at concentrations only slightly higher than the minimum inhibitory concentrations. Like benzylpenicillin, 6-aminopenicillanic acid appears to interfere with cell wall formation. Staphylococci trained to be resistant to 6-aminopenicillanic acid show resistance to benzyl­penicillin and vice versa.

scholarly journals Chromone Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Penicillium erubescens KUFA0220 and Their Antibacterial Activity

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 289 ◽  
Author(s):  
Decha Kumla ◽  
José Pereira ◽  
Tida Dethoup ◽  
Luis Gales ◽  
Joana Freitas-Silva ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Growth Inhibition ◽  
Marine Sponge ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Chromone Derivatives ◽  
Gram Positive Bacteria ◽  
Resistant Strains

A previously unreported chromene derivative, 1-hydroxy-12-methoxycitromycin (1c), and four previously undescribed chromone derivatives, including pyanochromone (3b), spirofuranochromone (4), 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromene-5-carboxylic acid (5), a pyranochromone dimer (6) were isolated, together with thirteen known compounds: β-sitostenone, ergosterol 5,8-endoperoxide, citromycin (1a), 12-methoxycitromycin (1b), myxotrichin D (1d), 12-methoxycitromycetin (1e), anhydrofulvic acid (2a), myxotrichin C (2b), penialidin D (2c), penialidin F (3a), SPF-3059-30 (7), GKK1032B (8) and secalonic acid A (9), from cultures of the marine sponge- associated fungus Penicillium erubescens KUFA0220. Compounds 1a–e, 2a, 3a, 4, 7–9, were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only 8 exhibited an in vitro growth inhibition of all Gram-positive bacteria whereas 9 showed growth inhibition of methicillin-resistant Staphyllococus aureus (MRSA). None of the compounds were active against Gram-negative bacteria tested.

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