scholarly journals A new phenothiazine derivate is active against Clostridioides difficile and shows low cytotoxicity

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258207
Author(s):  
Troels Ronco ◽  
Francisca Maria Aragao ◽  
Lasse Saaby ◽  
Jørn B. Christensen ◽  
Anders Permin ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Experimental Studies ◽  
Clinical Importance ◽  
Oral Exposure ◽  
Minimal Bactericidal Concentration ◽  
Phenothiazine Derivative ◽  
Minimal Inhibition Concentration ◽  
Clostridioides Difficile ◽  
Intestinal Pathogens

The rapid evolution of antibiotic resistance in Clostridioides difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matters of concern for public health. Thioridazine, a compound belonging to the phenothiazine group, has previous shown antimicrobial activity against C. difficile. The purpose of this present study was to investigate the potential of a novel phenothiazine derivative, JBC 1847, as an oral antimicrobial for treatment of intestinal pathogens and CDIs. The minimal inhibition concentration and the minimum bactericidal concentration of JBC 1847 against C. difficile ATCC 43255 were determined 4 μg/mL and high tolerance after oral administration in mice was observed (up to 100 mg/kg bodyweight). Pharmacokinetic modeling was conducted in silico using GastroPlusTM, predicting low (< 10%) systemic uptake after oral exposure and corresponding low Cmax in plasma. Impact on the intestinal bacterial composition after four days of treatment was determined by 16s rRNA MiSeq sequencing and revealed only minor impact on the microbiota in non-clinically affected mice, and there was no difference between colony-forming unit (CFU)/gram fecal material between JBC 1847 and placebo treated mice. The cytotoxicity of the compound was assessed in Caco-2 cell-line assays, in which indication of toxicity was not observed in concentrations up to seven times the minimal bactericidal concentration. In conclusion, the novel phenothiazine derivative demonstrated high antimicrobial activity against C. difficile, had low predicted gastrointestinal absorption, low intestinal (in vitro) cytotoxicity, and only induced minor changes of the healthy microbiota, altogether supporting that JBC 1847 could represent a novel antimicrobial candidate. The clinical importance hereof calls for future experimental studies in CDI models.

scholarly journals ANTIMICROBIAL ACTIVITY STUDY OF NEW QUINAZOLIN-4(3H)-ONES AGAINST STAPHYLOCOCCUS AUREUS AND STREPTOCOCCUS PNEUMONIAE

2021 ◽  
Vol 9 (4) ◽  
pp. 318-329
Author(s):  
M. A. Samotrueva ◽  
A. A. Ozerov ◽  
A. A. Starikova ◽  
N. M. Gabitova ◽  
D. V. Merezhkina ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Streptococcus Pneumoniae ◽  
Active Sites ◽  
Wide Spectrum ◽  
Experimental Studies ◽  
Amide Group ◽  
Pharmacological Effect ◽  
Dilution Method

Quinazolin-4(3H)-one derivatives exhibiting a wide spectrum of a pharmacological activity, represent a promising class of substances used to obtain antibacterial agents, which is especially important in the context of the emergence of pathogenic microorganisms’ resistance to drugs used in medicine. It has been proved that compounds having a naphthyl radical in the molecule, as well as an amide group bound to the benzene ring as quinazolinone substituents, are characterized by a pronounced antimicrobial activity against Staphylococcus aureus and Streptococcus pneumoniae.The aim of the research is a primary microbiological screening of the in vitro antimicrobial activity of new quinazolin-4(3H)-one derivatives against Staphylococcus aureus and Streptococcus pneumoniae, as well as the assessment of the relationship between the pharmacological effect and the structural transformation of the substance molecule, lipophilicity and the possibility of forming resistance to them.Materials and methods. The experimental studies have been carried out using well-known nosocomial pathogens of infectious and inflammatory diseases Staphylococcus aureus and Streptococcus pneumoniae by a serial dilution method.Results. A compound containing a naphthyl radical in its structure, which contributes to an increase in the hydrophobicity of the substance and its solubility in the membrane of a bacterial cell, has a bacteriostatic effect against both Staphylococcus aureus and Streptococcus pneumoniae. A similar pharmacological effect is exhibited by a derivative with an amide group as a substituent of the quinazolinone nucleus linked to a phenyl radical, which probably contributes to an increase in the degree of binding to active sites of enzymes involved in the DNA replication, and protein synthesis. Obviously, the increased lipophilicity, which promotes better binding to the efflux protein, cannot serve as objective characteristics of the emergence possibility of the pathogen’s resistance to this substance.Conclusion. Among the synthesized compounds, the leading substances that exhibit an antimicrobial activity against Staphylococcus aureus and Streptococcus pneumonia, have been identified. The assessment of the chemical structure made it possible to substantiate their pharmacological action and draw conclusions about the possibility of developing resistance to it in microbial cells.

scholarly journals In Silico and In Vitro Experimental Studies of New Dibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 321 ◽  
Author(s):  
Ilinca Margareta Vlad ◽  
Diana Camelia Nuta ◽  
Cornel Chirita ◽  
Miron Teodor Caproiu ◽  
Constantin Draghici ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Experimental Studies ◽  
In Silico Analysis ◽  
Maximum Tolerated Dose ◽  
In Vitro Cytotoxicity ◽  
Cell Membrane Permeability ◽  
Biofilm Growth

In a drug-repurposing-driven approach for speeding up the development of novel antimicrobial agents, this paper presents for the first time in the scientific literature the synthesis, physico-chemical characterization, in silico analysis, antimicrobial activity against bacterial and fungal strains in planktonic and biofilm growth state, as well as the in vitro cytotoxicity of some new 6,11-dihydrodibenz[b,e]oxepin-11(6H)one O-(arylcarbamoyl)oximes. The structures of intermediary and final substances (compounds 7a–j) were confirmed by 1H-NMR, 13C-NMR and IR spectra, as well as by elemental analysis. The in silico bioinformatic and cheminformatic studies evidenced an optimal pharmacokinetic profile for the synthesized compounds 7a–j, characterized by an average lipophilic character predicting good cell membrane permeability and intestinal absorption; low maximum tolerated dose for humans; potassium channels encoded by the hERG I and II genes as potential targets and no carcinogenic effects. The obtained compounds exhibited a higher antimicrobial activity against the planktonic Gram-positive Staphylococcus aureus and Bacillus subtilis strains and the Candida albicans fungal strain. The obtained compounds also inhibited the ability of S. aureus, B. subtilis, Escherichia coli and C. albicans strains to colonize the inert substratum, accounting for their possible use as antibiofilm agents. All the active compounds exhibited low or acceptable cytotoxicity levels on the HCT8 cells, ensuring the potential use of these compounds for the development of new antimicrobial drugs with minimal side effects on the human cells and tissues.

scholarly journals Detachment Characteristics and Oxacillin Resistance of Staphyloccocus aureus Biofilm Emboli in an In Vitro Catheter Infection Model

2004 ◽  
Vol 186 (14) ◽  
pp. 4486-4491 ◽  
Author(s):  
C. A. Fux ◽  
S. Wilson ◽  
P. Stoodley
Keyword(s):  
Stationary Phase ◽  
Clinical Importance ◽  
Bloodstream Infections ◽  
High Rate ◽  
Infection Model ◽  
Minimal Bactericidal Concentration ◽  
Catheter Infection ◽  
Oxacillin Resistance ◽  
Wide Range

ABSTRACT Catheter-related bloodstream infections due to Staphylococcus aureus are of increasing clinical importance. The pathophysiological steps leading to colonization and infection, however, are still incompletely defined. We observed growth and detachment of S. aureus biofilms in an in vitro catheter-infection model by using time-lapse microscopy. Biofilm emboli were characterized by their size and their susceptibility for oxacillin. Biofilm dispersal was found to be a dynamic process in which clumps of a wide range of diameters detach. Large detached clumps were highly tolerant to oxacillin compared with exponential-phase planktonic cultures. Interestingly, the degree of antibiotic tolerance in stationary-phase planktonic cultures was equal to that in the large clumps. The mechanical disruption of large clumps reduced the minimal bactericidal concentration (MBC) by more than 1,000 times. The MBC for whole biofilm effluent, consisting of particles with an average number of 20 bacteria was 3.5 times higher than the MBC for planktonic cultures. We conclude that the antibiotic resistance of detached biofilm particles depends on the embolus size and could be attributed to nutrient-limited stationary-phase physiology of cells within the clumps. We hypothesize that the detachment of multicellular clumps may explain the high rate of symptomatic metastatic infections seen with S. aureus.

scholarly journals The In Vitro and In Vivo Synergistic Antimicrobial Activity Assessment of Vacuum Microwave Assisted Aqueous Extracts from Pomegranate and Avocado Fruit Peels and Avocado Seeds Based on a Mixtures Design Model

Plants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1757
Author(s):  
Prodromos Skenderidis ◽  
Stefanos Leontopoulos ◽  
Konstantinos Petrotos ◽  
Chrysanthi Mitsagga ◽  
Ioannis Giavasis
Keyword(s):  
Antimicrobial Activity ◽  
Optical Density ◽  
Density Measurement ◽  
Design Model ◽  
Penicillium Expansum ◽  
Total Phenolic ◽  
Natural Food ◽  
Minimal Bactericidal Concentration

The present study aimed to assess the antimicrobial properties of encapsulated lyophilized powdered extracts of pomegranate peels (PP), avocado peels (AP) and avocado seeds (AS) in vitro and in vivo. Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) methods, optical density measurement, and well diffusion assay were used to determine antimicrobial activity against food borne bacteria (Gram− Escherichia coli, Salmonella typhimurium, Campylobacter jejuni, Pseudomonas putida), (Gram+ Staphylococcus aureus, Listeria monocytogenes, Clostridium perfringens, Lactobacillus plantarum), and fungi (Penicillium expansum and Aspergillus niger) based on a mixture design model. Additionally, the most effective powder was studied in vivo in yogurt, cream cheese, and minced meat burger. The samples that contained high polyphenol content also exhibited higher antioxidant, antimicrobial, and antifungal activity. From the results of the well diffusion, the MIC/MBC, and the cell optical density assays, the antimicrobial activity of the extracts was found to be correlated to the total phenolic content (TPC) of the samples and the type of the microorganism. The pomegranate peels extract presented the higher TPC and antioxidant activity and constitute the highest percentage in the most active antimicrobial mixture. The powders that were tested in vitro showed microbial type-dependent effects in each food model. The results presented here can be further studied in the large-scale industrial production of natural food preservatives.

scholarly journals In Vitro Antimicrobial Activity of GSQ1530, a New Heteroaromatic Polycyclic Compound

2002 ◽  
Vol 46 (10) ◽  
pp. 3168-3174 ◽  
Author(s):  
Yigong Ge ◽  
Stacey Difuntorum ◽  
Sofia Touami ◽  
Ian Critchley ◽  
Roland Bürli ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Therapeutic Potential ◽  
Clinical Isolates ◽  
In Vivo Studies ◽  
Cross Resistance ◽  
Minimal Bactericidal Concentration ◽  
Gram Positive ◽  
In Vitro Antimicrobial Activity

ABSTRACT GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were coevaluated against 215 clinical isolates. The MICs at which 90% of isolates are inhibited (MIC90s) of GSQ1530 for methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) were 2 and 4 μg/ml, respectively. The MIC90s of GSQ1530 for the streptococci tested were 2 μg/ml or less, regardless of their susceptibilities to other antibiotics. The MIC90 of GSQ1530 for the enterococci tested (including vancomycin-resistant enterococci) was 4 μg/ml. No cross-resistance was found between GSQ1530 and other known antibiotics. In a separate assay, GSQ1530 demonstrated excellent activity against vancomycin-intermediate-susceptible staphylococci (MIC90, 1 μg/ml). The minimal bactericidal concentration test was conducted with 73 clinical isolates; GSQ1530 was cidal against streptococci and staphylococci but static against enterococci. An in vitro killing kinetic study revealed a time-dependent profile, with at least a 3-log reduction of bacterial growth within 6 h after exposure to four times the MICs of GSQ1530 for both S. aureus and Streptococcus pneumoniae. The checkerboard study showed that GSQ1530 had a synergistic interaction with rifampin against MRSA. The test medium was found to have little effect on in vitro antimicrobial potency. The MICs of GSQ1530 for gram-positive cocci were 4- to 32-fold higher in the presence of serum proteins. GSQ1530 has high levels of plasma protein binding (91 and 89% for rat and human plasma, respectively). These preliminary results demonstrate that GSQ1530, a representative compound of our novel HARP antibiotics, has broad-spectrum activity against gram-positive bacteria. This novel class of antibacterial compounds is profiled in vivo to assess the therapeutic potential in humans. Ongoing in vivo studies will assess whether this class of molecules has promising in vivo efficacy and safety profiles.

scholarly journals Lactiplantibacillus plantarum strains isolated from spontaneously fermented cocoa exhibit potential probiotic properties against Gardnerella vaginalis and Neisseria gonorrhoeae

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nathan das Neves Selis ◽  
Hellen Braga Martins de Oliveira ◽  
Hiago Ferreira Leão ◽  
Yan Bento dos Anjos ◽  
Beatriz Almeida Sampaio ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Neisseria Gonorrhoeae ◽  
Clinical Importance ◽  
Gardnerella Vaginalis ◽  
Haemolytic Activity ◽  
Probiotic Properties ◽  
Vaginal Infections ◽  
Probiotic Potential

Abstract Background Probiotics are important tools in therapies against vaginal infections and can assist traditional antibiotic therapies in restoring healthy microbiota. Recent research has shown that microorganisms belonging to the genus Lactobacillus have probiotic potential. Thus, this study evaluated the potential in vitro probiotic properties of three strains of Lactiplantibacillus plantarum, isolated during the fermentation of high-quality cocoa, against Gardnerella vaginalis and Neisseria gonorrhoeae. Strains were evaluated for their physiological, safety, and antimicrobial characteristics. Results The hydrophobicity of L. plantarum strains varied from 26.67 to 91.67%, and their autoaggregation varied from 18.10 to 30.64%. The co-aggregation of L. plantarum strains with G. vaginalis ranged from 14.73 to 16.31%, and from 29.14 to 45.76% with N. gonorrhoeae. All L. plantarum strains could moderately or strongly produce biofilms. L. plantarum strains did not show haemolytic activity and were generally sensitive to the tested antimicrobials. All lactobacillus strains were tolerant to heat and pH resistance tests. All three strains of L. plantarum showed antimicrobial activity against the tested pathogens. The coincubation of L. plantarum strains with pathogens showed that the culture pH remained below 4.5 after 24 h. All cell-free culture supernatants (CFCS) demonstrated activity against the two pathogens tested, and all L. plantarum strains produced hydrogen peroxide. CFCS characterisation in conjunction with gas chromatography revealed that organic acids, especially lactic acid, were responsible for the antimicrobial activity against the pathogens evaluated. Conclusion The three strains of L. plantarum presented significant probiotic characteristics against the two pathogens of clinical importance. In vitro screening identified strong probiotic candidates for in vivo studies for the treatment of vaginal infections.

scholarly journals Composition and antimicrobial activity of essential oil of yarrow (Achillea millefolium L.)

2020 ◽  
pp. 545-550
Author(s):  
Paulo Sergio Daniel ◽  
Emerson Luiz Botelho Lourenço ◽  
Rayane Monique Sete da Cruz ◽  
Carlos Henrique De Souza Gonçalves ◽  
Luiz Renato Marques Das Almas ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oil ◽  
Gas Chromatography Mass Spectrometry ◽  
Achillea Millefolium ◽  
Chemical Components ◽  
Minimal Bactericidal Concentration ◽  
Microdilution Method ◽  
Anti Oxidant ◽  
Micro Organisms

The medicinal plant yarrow (Achillea millefolium L.) belongs to the Asteracea family. It is being used in the pharmacological, food, and cosmetic industry. The economic importance of yarrow resides in its essential oil (EO). This plant is used in traditional medicine as the EO has properties which range from antibacterial, antifungal, anti-inflammatory, anti-oxidant and antitumor activities. The objective of this study was to identify chemical components and EO content of yarrow, as well as its antimicrobial activity against some micro-organisms in vitro. The fresh leaves were collected in a morning in October (2018) at the UNIPAR Medicinal Plants Garden, Umuarama-Paraná State, Brazil. The EO was obtained by hydrodistillation of the modified Clevenger type. After that, the content (m/m%) was calculated. The chemical composition of the EO was identified by gas chromatography/mass spectrometry (GC/MS). The minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal fungicidal concentration (MFC) were determined by a microdilution method in 96-well microtitre plates and effect of EO was assessed on four micro-organisms (Candida albicans, Staphylococcus epidermidis, Escherechia coli and Klebsiella pneumoniae). The EO content (yield) in the plant shoots was 0.4% (four grams of EO kg-1 of plant fresh shoots) and presented 20 chemical compounds such as α-farnesene (31.66%), followed by chamazulene (17.17%), β-caryophyllene (10.27%) and sabinene (8.77%). The majority class was hydrocarbon sesquiterpene with 74.29%. The antimicrobial activity tests showed that the EO had low antimicrobial activity against the analyzed species with MIC for all species above 1.5 mg mL-1. It was concluded that the EO content was 0.4%. The major component was α-farnesene (31.66%) and EO presented low MIC.

scholarly journals Determination of In vitro antimicrobial activity of homeopathy medicines

2019 ◽  
Vol 8 (1) ◽  
pp. 7-9
Author(s):  
Soyoda Mokarroma ◽  
Tahmina Shammi
Keyword(s):  
Antimicrobial Activity ◽  
Mechanism Of Action ◽  
Bactericidal Effect ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
Diffusion Technique ◽  
Intestinal Pathogens ◽  
Homeopathic Remedies ◽  
Homeopathic Drugs

Homeopathy is a popular alternative medicine. The mechanism of action of homeopathic drug has not been clarified but it has been found to be effective against various diseases including diarrhea, dysentery, otitis media, eczema and even cancer. After qualifying thorough investigation, it can be used against antibiotic tolerance and multi drug resistant bacteria. In a recent study, bactericidal effect of homeopathic remedies has been investigated. But such an effect is not in accordance with the general principles of homeopathy. To test this paradigm, in vitro antimicrobial effects of four homeopathic drugs Aconite 30, Arsenicum album 30, Mercuric corrosivus 30 and Mercury solution 200 against five common intestinal pathogens, including- Escherichia coli, Klebsiella sp., Salmonella sp. Pseudomonas sp., and Bacillus sp have been observed. Standard agar well diffusion technique and macrodilution technique were followed. But, tested homeopathic drugs did not show any significant effect on any of the five pathogens. Rigorous study against other organism is required to fully understand antimicrobial activity and other mechanism of action. Stamford Journal of Microbiology, Vol.8(1) 2018: 7-9

scholarly journals In vitro antimicrobial activity of Salvadora persica extract on Helicobacter pylori strains isolated from duodenal ulcer biopsies

2012 ◽  
Vol 3 (1) ◽  
pp. 9 ◽  
Author(s):  
Ehsan Mirkamandar ◽  
Mohammad Reza Shakibaie ◽  
Saeed Adeli ◽  
Mitra Mehrabani ◽  
Mohammad Mehdi Hayatbakhsh ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Dilution Method ◽  
Minimal Bactericidal Concentration ◽  
Agar Dilution Method ◽  
Zone Of Inhibition ◽  
Salvadora Persica ◽  
H Pylori

The aim of this study was to evaluate the <em>in vitro</em> antimicrobial activity of a methanolic extract of <em>Salvadora persica</em> solution on <em>Helicobacter pylori</em> isolated from duodenal ulcer. Over 22 strains of H. pylori were isolated from duodenal ulcer from August 2010 to June 2011. The <em>S. persica</em> stem was purchased from a local herb market and finely powdered. Extraction was performed with 60% methanol using a soxhlet extractor for 48 h until the solvent turned colorless while being incubated in an oven at 40°C for 48 h till dried. Dry powder was used to determine antimicrobial activity by the agar ditch method. Minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extract were determined by the agar dilution method. At concentrations of 10, 100, 200, 500 µg/mL, no zone of inhibition around the ditches was observed while a clear zone of inhibition (12 mm) was detected at 1000 µg/mL concentration for all the isolates. The best antimicrobial activity was observed at MIC 1000 µg/mL (P≤0.05). Furthermore, 10 out of 22 isolates were inhibited at 750 µg/mL of the extract. The MBC results showed that at a concentration of 1000 µg/mL all cells were dead while at a concentration of 750 µg/mL of<em> S. persica </em>a few <em>H. pylori</em> cells were still able to form colonies on Brucella agar supplemented with sheep red blood cells and antibiotics. From the above results it can be concluded that high concentration of S.persica could inhibit the growth of H. pylori and MIC and MBC were similar at that concentration.

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