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Efficacy of two novel 2,2'-bifurans to inhibit methicillin-resistant Staphylococcus aureus infection in male mice in comparison to vancomycin.

El-Sayed WM, Hussin WA, Ismail MA - Drug Des Devel Ther (2012)

Bottom Line: Treatment with bifurans did not cause any toxicity.Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen.Similar to vancomycin, bifurans ameliorated most of the previous effects.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Sciences and Chemistry, King Faisal University, Al-Hofuf, Saudi Arabia. waelelhalawany@hotmail.com

ABSTRACT
The therapeutic efficacy of two novel bifurans and vancomycin in an animal model of a methicillin-resistant Staphylococcus aureus (MRSA) infection was compared. Adult male CF-1 mice (25-35 g) were intraperitoneally injected with 200 μL/mouse containing 10(7) cell-forming units of MRSA. After 16 hours, animals were treated with 110 mg/kg of vancomycin, or 5 mg/kg of mononitrile bifuran (1A) or monocationic bifuran (1B) and killed after 8 hours. Treatment with bifurans did not cause any toxicity. Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen. Colonies recovered from livers and kidneys of mice injected with 1A or 1B lost the initial resistance pattern and became susceptible to methicillin and ciprofloxacin. MRSA elevated the serum urea level and activities of alanine aminotransferase and γ-glutamyl transpeptidase. MRSA also elevated the hepatic level of malondialdehyde, and serum levels of tumor necrosis factor and interleukin-6. MRSA also reduced the glutathione content and activities of catalase and glutathione S-transferase in liver. Similar to vancomycin, bifurans ameliorated most of the previous effects. Compound 1B was superior to 1A, and sometimes both provided better antistaphylococcal agents than vancomycin against MRSA pathogenesis. The present findings along with our previous studies support further evaluation of the efficacy of these bifurans in clinical studies.

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Related in: MedlinePlus

Bifuran derivatives as antibacterial agents; mononitrile bifuran (A) and monocationic bifuran (B).
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f1-dddt-6-279: Bifuran derivatives as antibacterial agents; mononitrile bifuran (A) and monocationic bifuran (B).

Mentions: Adult male CF-1 mice (25–35 g) were obtained from the Faculty of Veterinary Medicine, King Faisal University, and were maintained in a humidity- and temperature-controlled environment on a 12-hour light/dark cycle with continuous free access to food and water. The mice were divided into seven groups, with five mice each. The first group (naïve) was injected with isotonic saline. Groups two and three were intraperitoneally injected with a single dose of either mononitrile bifuran (Figure 1A) or monocationic bifuran (Figure 1B) at 5 mg/kg and killed after 8 hours. Groups 4–7 were injected with 200 μL/mouse containing 107 CFU of MRSA ATCC 33593 (MRSA). After 16 hours postinfection, groups 5–7 were injected intraperitoneally with either 110 mg/kg of vancomycin8 or bifurans 1A or 1B at 5 mg/kg. After 8 hours posttreatment, all animals were sacrificed. Blood was collected and serum was immediately prepared, and the livers were quickly perfused in situ with ice-cold saline. The gallbladder was then carefully dissected away, and the remaining liver was homogenized in ice-cold buffer and subjected to centrifugation (9000 × g for 15 minutes), and the supernatant was collected. Protein content of the supernatant and serum was determined using Folin–Ciocalteu phenol reagent (Sigma), as described by Lowry et al,9 and both were stored at −80°C until assayed for enzyme activity. All animal procedures were approved by the King Faisal University Ethics and Animal Care Committee and were conducted in agreement with National Institutes of Health guidelines for the humane care of laboratory animals.


Efficacy of two novel 2,2'-bifurans to inhibit methicillin-resistant Staphylococcus aureus infection in male mice in comparison to vancomycin.

El-Sayed WM, Hussin WA, Ismail MA - Drug Des Devel Ther (2012)

Bifuran derivatives as antibacterial agents; mononitrile bifuran (A) and monocationic bifuran (B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3472655&req=5

f1-dddt-6-279: Bifuran derivatives as antibacterial agents; mononitrile bifuran (A) and monocationic bifuran (B).
Mentions: Adult male CF-1 mice (25–35 g) were obtained from the Faculty of Veterinary Medicine, King Faisal University, and were maintained in a humidity- and temperature-controlled environment on a 12-hour light/dark cycle with continuous free access to food and water. The mice were divided into seven groups, with five mice each. The first group (naïve) was injected with isotonic saline. Groups two and three were intraperitoneally injected with a single dose of either mononitrile bifuran (Figure 1A) or monocationic bifuran (Figure 1B) at 5 mg/kg and killed after 8 hours. Groups 4–7 were injected with 200 μL/mouse containing 107 CFU of MRSA ATCC 33593 (MRSA). After 16 hours postinfection, groups 5–7 were injected intraperitoneally with either 110 mg/kg of vancomycin8 or bifurans 1A or 1B at 5 mg/kg. After 8 hours posttreatment, all animals were sacrificed. Blood was collected and serum was immediately prepared, and the livers were quickly perfused in situ with ice-cold saline. The gallbladder was then carefully dissected away, and the remaining liver was homogenized in ice-cold buffer and subjected to centrifugation (9000 × g for 15 minutes), and the supernatant was collected. Protein content of the supernatant and serum was determined using Folin–Ciocalteu phenol reagent (Sigma), as described by Lowry et al,9 and both were stored at −80°C until assayed for enzyme activity. All animal procedures were approved by the King Faisal University Ethics and Animal Care Committee and were conducted in agreement with National Institutes of Health guidelines for the humane care of laboratory animals.

Bottom Line: Treatment with bifurans did not cause any toxicity.Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen.Similar to vancomycin, bifurans ameliorated most of the previous effects.

View Article: PubMed Central - PubMed

Affiliation: Departments of Biological Sciences and Chemistry, King Faisal University, Al-Hofuf, Saudi Arabia. waelelhalawany@hotmail.com

ABSTRACT
The therapeutic efficacy of two novel bifurans and vancomycin in an animal model of a methicillin-resistant Staphylococcus aureus (MRSA) infection was compared. Adult male CF-1 mice (25-35 g) were intraperitoneally injected with 200 μL/mouse containing 10(7) cell-forming units of MRSA. After 16 hours, animals were treated with 110 mg/kg of vancomycin, or 5 mg/kg of mononitrile bifuran (1A) or monocationic bifuran (1B) and killed after 8 hours. Treatment with bifurans did not cause any toxicity. Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen. Colonies recovered from livers and kidneys of mice injected with 1A or 1B lost the initial resistance pattern and became susceptible to methicillin and ciprofloxacin. MRSA elevated the serum urea level and activities of alanine aminotransferase and γ-glutamyl transpeptidase. MRSA also elevated the hepatic level of malondialdehyde, and serum levels of tumor necrosis factor and interleukin-6. MRSA also reduced the glutathione content and activities of catalase and glutathione S-transferase in liver. Similar to vancomycin, bifurans ameliorated most of the previous effects. Compound 1B was superior to 1A, and sometimes both provided better antistaphylococcal agents than vancomycin against MRSA pathogenesis. The present findings along with our previous studies support further evaluation of the efficacy of these bifurans in clinical studies.

Show MeSH
Related in: MedlinePlus