scholarly journals Design, Synthesis and Biological Evaluation of Biphenylglyoxamide-Based Small Molecular Antimicrobial Peptide Mimics as Antibacterial Agents

2020 ◽  
Vol 21 (18) ◽  
pp. 6789
Author(s):  
Tsz Tin Yu ◽  
Rajesh Kuppusamy ◽  
Muhammad Yasir ◽  
Md. Musfizur Hassan ◽  
Amani Alghalayini ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Quaternary Ammonium ◽  
Lipid Membranes ◽  
Bacterial Infections ◽  
Biological Evaluation ◽  
In Vitro Toxicity ◽  
Ammonium Iodide ◽  
Gram Positive ◽  
Gram Negative

There has been an increasing interest in the development of antimicrobial peptides (AMPs) and their synthetic mimics as a novel class of antibiotics to overcome the rapid emergence of antibiotic resistance. Recently, phenylglyoxamide-based small molecular AMP mimics have been identified as potential leads to treat bacterial infections. In this study, a new series of biphenylglyoxamide-based small molecular AMP mimics were synthesised from the ring-opening reaction of N-sulfonylisatin bearing a biphenyl backbone with a diamine, followed by the conversion into tertiary ammonium chloride, quaternary ammonium iodide and guanidinium hydrochloride salts. Structure–activity relationship studies of the analogues identified the octanesulfonyl group as being essential for both Gram-positive and Gram-negative antibacterial activity, while the biphenyl backbone was important for Gram-negative antibacterial activity. The most potent analogue was identified to be chloro-substituted quaternary ammonium iodide salt 15c, which possesses antibacterial activity against both Gram-positive (MIC against Staphylococcus aureus = 8 μM) and Gram-negative bacteria (MIC against Escherichia coli = 16 μM, Pseudomonas aeruginosa = 63 μM) and disrupted 35% of pre-established S. aureus biofilms at 32 μM. Cytoplasmic membrane permeability and tethered bilayer lipid membranes (tBLMs) studies suggested that 15c acts as a bacterial membrane disruptor. In addition, in vitro toxicity studies showed that the potent compounds are non-toxic against human cells at therapeutic dosages.

Efficient Synthesis and Antibacterial Profile of Bis(2-hydroxynaphthalene- 1,4-dione)

2020 ◽  
Vol 20 (2) ◽  
pp. 121-131 ◽  
Author(s):  
Juliana S. Novais ◽  
Aline C. Rosandiski ◽  
Carolina M. de Carvalho ◽  
Letícia S. de Saules Silva ◽  
Lais C. dos S. Velasco de Souza ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Public Health Problem ◽  
In Vitro Toxicity ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Healthy Human ◽  
Gram Negative ◽  
Methicillin Resistant

Background: Antibacterial resistance is a serious public health problem infecting millions in the global population. Currently, there are few antimicrobials on the market against resistant bacterial infections. Therefore, there is an urgent need for new therapeutic options against these strains. Objective: In this study, we synthesized and evaluated ten Bis(2-hydroxynaphthalene-1,4-dione) against Gram-positive strains, including a hospital Methicillin-resistant (MRSA), and Gram-negative strains. Method: The compounds were prepared by condensation of aldehydes and lawsone in the presence of different L-aminoacids as catalysts in very good yields. The compounds were submitted to antibacterial analysis through disk diffusion and Minimal Inhibitory Concentration (MIC) assays. Result: L-aminoacids have been shown to be efficient catalysts in the preparation of Bis(2- hydroxynaphthalene-1,4-dione) from 2-hydroxy-1,4-naphthoquinones and arylaldehydes in excellent yields of up to 96%. The evaluation of the antibacterial profile against Gram-positive strains (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228) also including a hospital Methicillin-resistant S. aureus (MRSA) and Gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Klebsiella pneumoniae ATCC 4352), revealed that seven compounds showed antibacterial activity within the Clinical and Laboratory Standards Institute (CLSI) levels mainly against P. aeruginosa ATCC 27853 (MIC 8-128 µg/mL) and MRSA (MIC 32-128 µg/mL). In addition, the in vitro toxicity showed all derivatives with no hemolytic effects on healthy human erythrocytes. Furthermore, the derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) parameters, and a similar profile to antibiotics currently in use. Finally, the in silico evaluation pointed to a structure-activity relationship related to lipophilicity for these compounds. This feature may help them in acting against Gram-negative strains, which present a rich lipid cell wall selective for several antibiotics. Conclusion: Our data showed the potential of this series for exploring new and more effective antibacterial activities in vivo against other resistant bacteria.

scholarly journals TSPphg Lysin from the Extremophilic Thermus Bacteriophage TSP4 as a Potential Antimicrobial Agent against Both Gram-Negative and Gram-Positive Pathogenic Bacteria

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 192 ◽  
Author(s):  
Feng Wang ◽  
Xinyu Ji ◽  
Qiupeng Li ◽  
Guanling Zhang ◽  
Jiani Peng ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Infection Model ◽  
Bacterial Cells ◽  
Skin Damage ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Gram Negative

New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 μg/mL TSPphg treatment at 37 °C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.

scholarly journals Antibacterial Potential of Aloe weloensis (Aloeacea) Leaf Latex against Gram-Positive and Gram-Negative Bacteria Strains

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Yohannes Kelifa Emiru ◽  
Ebrahim Abdela Siraj ◽  
Tekleab Teka Teklehaimanot ◽  
Gedefaw Getnet Amare
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Inhibition Zone ◽  
Antibacterial Activities ◽  
Maximum Activity ◽  
New Drugs ◽  
Diffusion Method ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative

Objective. To evaluate the antibacterial effects of the leaf latex of Aloe weloensis against infectious bacterial strains. Methods. The leaf latex of A. weloensis at different concentrations (400, 500, and 600 mg/ml) was evaluated for antibacterial activities using the disc diffusion method against some Gram-negative species such as Escherichia coli (ATCC 14700) and Pseudomonas aeruginosa (ATCC 35619) and Gram-positive such as Staphylococcus aureus (ATCC 50080) and Enterococcus fecalis (ATCC 4623). Results. The tested concentrations of the latex ranging between 400 and 600 mg·mL−1 showed significant antibacterial activity against bacterial strain. The highest dose (600 mg/ml) of A. weloensis leaf latex revealed the maximum activity (25.93 ± 0.066 inhibition zone) followed by the dose 500 mg/ml against S. aureus. The lowest antibacterial activity was observed by the concentration 400 mg/ml (5.03 ± 0.03) against E. coli. Conclusion. The results of the present investigation suggest that the leaf latex of A. weloensis can be used as potential leads to discover new drugs to control some bacterial infections.

scholarly journals DESIGN, SYNTHESIS, DOCKING STUDIES AND BIOLOGICAL EVALUATION OF 2-PHENYL-3-(SUBSTITUTED BENZO[d] THIAZOL-2-YLAMINO)-QUINAZOLINE-4(3H)-ONE DERIVATIVES AS ANTIMICROBIAL AGENTS

2018 ◽  
Vol 10 (10) ◽  
pp. 57
Author(s):  
Pooja Pisal ◽  
Meenakshi Deodhar ◽  
Amol Kale ◽  
Ganesh Nigade ◽  
Smita Pawar
Keyword(s):  
Antimicrobial Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Spectral Studies ◽  
Gram Negative Bacteria ◽  
Significant Activity ◽  
Fusion Reactions ◽  
Gram Positive ◽  
Gram Negative

Objective: A new series 2-phenyl-3-(substituted benzo[d] thiazol-2-ylamino)-quinazoline-4(3H)-one was prepared by the fusion method by reacting 2-phenyl benzoxazine with 2-hydrazino benzothiazole and it was evaluated for their antimicrobial activity against gram positive, gram negative bacteria and fungi.Methods: Titled compounds were synthesized by fusion reactions. These compounds were evaluated by in vitro antibacterial and antifungal activity using the minimum inhibitory concentration and zone of inhibition methods. The synthesized compounds were characterized with the help of infrared, NMR and mass spectral studies. The benzothiazole moiety and the quinazoline ring have previously shown DNA gyrase inhibition and target related antibacterial activity. Thus, molecular docking studies of synthesized compounds were carried out (PDB: 3G75) to study the possible interaction of compounds with the target. The batch grid docking was performed to determine the probable.Results: These compounds showed significant activity against gram positive and gram negative bacteria as well against the fungi. The compound A5 was found to be active against B. subtilis, P aeruginosa and C. albican at 12.5 µg/ml MIC. The compound A3 was found to be active against all microbial strains selected at 25 and 12.5 µg/ml MIC.Conclusion: Though the relationship between the activities shown by these compounds in, the antimicrobial study is still to be established, the docking studies conducted found to be consistent with antimicrobial results. Thus the results indicate that the designed structure can be a potential lead as an antimicrobial agent.

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.

scholarly journals Microwave Mediated Synthesis of Novel 1,3,5-Triazine Derivative and their Biological Evaluation

2021 ◽  
Vol 3 (12) ◽  
pp. 181-185
Author(s):  
Krishn Kumar Barmase ◽  
Deepak Basedia ◽  
Balkrishna Dubey
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Effect ◽  
Bacterial Species ◽  
Biological Evaluation ◽  
Chloride Ions ◽  
Gram Negative ◽  
Triazine Derivative ◽  
Triazine Derivatives ◽  
In Vitro Antibacterial Activity

1,3,5-Triazine derivative are synthesized by replacement of chloride ions of Cyanuric chloride and 1,3,5-Triazine derivative are showing promising biologically activity such as Antibacterial, Antifungal, Antimalarial, Antivirus, Anticancer that’s why interest of researches on synthesis of 1,3,5-Triazine derivatives always in focused. The present study reported the synthesis of 2,4,6-Trisubstituted 1,3,5-Triazine derivatives by Microwave mediated Method which gave the desired result in less time with higher yield. The structure of 1,3,5-Triazine derivatives have been elucidated by Spectral of IR, NMR and MASS. The derivative of 1,3,5-Triazine are evaluated for their In vitro Antibacterial activity against Gram Positive and Gram Negative Bacterial species and shown good Antibacterial effect.

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