scholarly journals Preliminary Insight of Pyrrolylated-Chalcones as New Anti-Methicillin-Resistant Staphylococcus aureus (Anti-MRSA) Agents

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5314
Author(s):  
Mohanapriya Gunasekharan ◽  
Tae-Ik Choi ◽  
Yaya Rukayadi ◽  
Muhammad Alif Mohammad Latif ◽  
Thiruventhan Karunakaran ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Docking Simulation ◽  
New Drugs ◽  
Zebrafish Model ◽  
Standard Drug ◽  
Methicillin Resistant ◽  
Bacterial Cell Death ◽  
Kill Curve

Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1–15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of −7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.

scholarly journals Trans-Cinnamaldehyde Exhibits Synergy with Conventional Antibiotic against Methicillin-Resistant Staphylococcus aureus

2021 ◽  
Vol 22 (5) ◽  
pp. 2752
Author(s):  
Shu Wang ◽  
Ok-Hwa Kang ◽  
Dong-Yeul Kwon
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Regulatory Gene ◽  
Western Blot Assay ◽  
Methicillin Resistant ◽  
Wide Range ◽  
Kill Curve ◽  
Conventional Antibiotics ◽  
Time Kill

Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide and has acquired multiple resistance to a wide range of antibiotics. Hence, there is a pressing need to explore novel strategies to overcome the increase in antimicrobial resistance. The present study aims to investigate the efficacy and mechanism of plant-derived antimicrobials, trans-cinnamaldehyde (TCA) in decreasing MRSA’s resistance to eight conventional antibiotics. A checkerboard dilution test and time–kill curve assay are used to determine the synergistic effects of TCA combined with the antibiotics. The results indicated that TCA increased the antibacterial activity of the antibiotics by 2-16-fold. To study the mechanism of the synergism, we analyzed the mecA transcription gene and the penicillin-binding protein 2a level of MRSA treated with TCA by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. Additionally, it was verified that TCA can significantly inhibit the biofilm, which is highly resistant to antibiotics. The expression of the biofilm regulatory gene hld of MRSA after TCA treatment was also significantly downregulated. These findings suggest that TCA maybe is an exceptionally potent modulator of antibiotics.

scholarly journals Antibacterial activity of Taxodium ascendens Diterpenes against Methicillin-resistant Staphylococcus aureus

2014 ◽  
Vol 9 (8) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Courtney M. Starks ◽  
Vanessa L. Norman ◽  
Russell B. Williams ◽  
Matt G. Goering ◽  
Stephanie M. Rice ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Methicillin Resistant

One new and seven known diterpenes were identified from an antibacterial chromatographic fraction of Taxodium ascendens. Of these, demethylcryptojaponol (2), 6-hydroxysalvinolone (3), hydroxyferruginol (4), and hinokiol (5) demonstrated potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). These compounds represent a class of synthetically accessible compounds that could be further developed for treatment of drug-resistant bacterial infections.

Toxicological and Antimicrobial Evaluations of Formulated Ointment from Eskwater (Mikania cordata Asteraceae) Leaf Extract against Trichophyton mentagrophytes and Methicillin-Resistant Staphylococcus aureus

10.17158/334 ◽  
2014 ◽  
Vol 18 (2) ◽  
Author(s):  
Judee N. Nogodula ◽  
Lady Ron M. Ducut ◽  
Jelah Mae F. Edorot ◽  
Aizovelle T. Egagamao
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Leaf Extract ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Trichophyton Mentagrophytes ◽  
Positive Control ◽  
Albino Rats ◽  
Standard Drug ◽  
Methicillin Resistant ◽  
Significant Difference

<p>Eskwater (Mikania cordata) is a medicinal plant in treating wounds by B’laan tribe. It is a useful treatment in the emerging cases of difficult-totreat infections caused by Methicillin-Resistant Staphylococcus aureus and Trichophyton mentagrophytes. To validate such claims, this study was conducted to assess the toxicological and antimicrobial properties of eskwater leaf extract through the acute dermal toxicity, antibacterial activity, Minimum Inhibitory Concentration (MIC), potency test with the standard drug and mutagenicity assay. Toxicity level was attained using female albino rats with the dose of 1000 mg/kg (Sighting study) while 1000 and 2000 mg/kg for Main study. Kirby-Bauer Method was employed for antibacterial activity using Vancomycin and Terbinafine as positive controls. MIC was determined in two-fold serial dilution and Ames test was employed for mutagenic assay using Salmonella typhimurium TA98. Hydrophilic base with low, medium and high doses were incorporated, respectively for ointment formulation. Results showed that eskwater extract was not toxic based from OECD 404 guideline and had partially active action against MRSA ATCC 43300 (13.66 ± 0.5778) and showed no inhibition in fungal growth. MIC was effective at 0.05 g/ml against MRSA only. It exhibited comparable potency with Vancomycin at the concentration of 0.32 mg and lastly, no noticeable mutagenic property was established. One-Way ANOVA and Post Hoc Tukey’s multiple comparison tests were employed in the efficacy of ointment. A significant difference resulted among the formulated ointment and positive control indicating that the three doses of formulated ointment and positive control have different potential to induce inhibition on the growth of MRSA. Ointment evaluated on its physical characteristics appeared greenish brown, has pH 6, good spreadability and washes out easily.</p>

scholarly journals Antibiofilm effects of N,O-acetals derived from 2-amino-1,4-naphthoquinone are associated with downregulation of important global virulence regulators in methicillin-resistant Staphylococcus aureus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Juliana Silva Novais ◽  
Mariana Fernandes Carvalho ◽  
Mariana Severo Ramundo ◽  
Cristiana Ossaille Beltrame ◽  
Reinaldo Barros Geraldo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Antimicrobial Resistance ◽  
Biofilm Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Biological Properties ◽  
New Drugs ◽  
Strong Impact ◽  
Methicillin Resistant ◽  
Great Demand

AbstractDespite the existing antibiotics, antimicrobial resistance is a major challenge. Consequently, the development of new drugs remains in great demand. Quinones is part of a broad group of molecules that present antibacterial activity besides other biological properties. The main purpose of this study was to evaluate the antibiofilm activities of synthetic N,O-acetals derived from 2-amino-1,4-naphthoquinone [7a: 2-(methoxymethyl)-amino-1,4-naphthoquinone; 7b: 2-(ethoxymethyl)-amino-1,4-naphthoquinone; and 7c: 2-(propynyloxymethyl)-amino-1,4-naphthoquinone] against methicillin-resistant Staphylococcus aureus (MRSA). The derivatives 7b and 7c, specially 7b, caused strong impact on biofilm accumulation. This inhibition was linked to decreased expression of the genes fnbA, spa, hla and psmα3. More importantly, this downregulation was paralleled by the modulation of global virulence regulators. The substitution of 2-ethoxymethyl (7b) in comparison with 2-propynyloxymethyl (7c) enhanced sarA-agr inhibition, decreased fnbA transcripts (positively regulated by sarA) and strongly impaired biofilm accumulation. Indeed, 7b triggered intensive autolysis and was able to eliminate vancomycin-persistent cells. Consequently, 7b is a promising molecule displaying not only antimicrobial effects, but also antibiofilm and antipersistence activities. Therefore, 7b is a good candidate for further studies involving the development of novel and more rational antimicrobials able to act in chronic and recalcitrant infections, associated with biofilm formation.

scholarly journals An antidote for Staphylococcus aureus pneumonia?

2008 ◽  
Vol 205 (2) ◽  
pp. 271-274 ◽  
Author(s):  
Frank R. DeLeo ◽  
Michael Otto
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
The United States ◽  
Vaccine Strategy ◽  
Methicillin Resistant ◽  
Successful Vaccine ◽  
Staphylococcal Pneumonia ◽  
Staphylococcus Aureus Pneumonia

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bacterial infections in the United States. Severe invasive MRSA infections, which include pneumonia, are difficult to treat because the bacteria are resistant to antibiotics. A new report now shows that immunization against α-hemolysin (Hla), a cytolytic toxin secreted by most S. aureus strains, protects mice against lethal pneumonia. This finding represents the first successful vaccine strategy for the treatment of staphylococcal pneumonia.

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