Synergy of aminoglycoside antibiotics by 3-Benzylchroman derivatives from the Chinese drug Caesalpinia sappan against clinical methicillin-resistant Staphylococcus aureus (MRSA).

Abstract

The in vitro antimicrobial activities of three 3-Benzylchroman derivatives, i.e. Brazilin (1), Brazilein (2) and Sappanone B (3) from Caesalpinia sappan L. (Leguminosae) were assayed, which mainly dealt with synergistic evaluation of aminoglycoside and other type of antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by the three compounds through the Chequerboard and Time-kill curve methods. The results showed that Compounds 1-3 alone exhibited moderate to weak activity against methicillin-susceptible S. aureus (MSSA) and other standard strains by MICs/MBCs ranged from 32/64 to >1024/>1024 μg/ml, with the order of activity as 1>2>3. Chequerboard method showed significant anti-MRSA synergy of 1/Aminoglycosides (Gentamicin, Amikacin, Etimicin and Streptomycin) combinations with (FICIs)50 at 0.375-0.5. The combined (MICs)50 values (μg/ml) reduced from 32-128/16-64 to 4-8/4-16, respectively. The percent of reduction by MICs ranged from 50% to 87.5%, with a maximum of 93.8% (1/16 of the alone MIC). Combinations of 2 and 3 with Aminoglycosides and the other antibiotics showed less potency of synergy. The dynamic Time-killing experiment further demonstrated that the combinations of 1/aminoglycoside were synergistically bactericidal against MRSA. The anti-MRSA synergy results of the bacteriostatic (Chequerboard method) and bactericidal (time-kill method) efficiencies of 1/Aminoglycoside combinations was in good consistency, which made the resistance reversed by CLSI guidelines. We concluded that the 3-Benzylchroman derivative Brazilin (1) showed in vitro synergy of bactericidal activities against MRSA when combined with Aminoglycosides, which might be beneficial for combinatory therapy of MRSA infection.

• Authors: G Y Zuo, Z Q Han, X Y Hao, J Han, Z S Li, G C Wang
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 21 Issue 7 Pg. 936-41 (Jun 15 2014) ISSN: 1618-095X [Electronic] Germany
• PMID: 24703330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014. Published by Elsevier GmbH.

Chemical References

• Aminoglycosides
• Anti-Bacterial Agents
• Benzopyrans
• Chromans
• Drugs, Chinese Herbal
• Indenes
• sappanone B
• brazilein
• brazilin

Topics

• Aminoglycosides (chemistry, pharmacology)
• Anti-Bacterial Agents (chemistry, pharmacology)
• Benzopyrans (chemistry, pharmacology)
• Caesalpinia (chemistry)
• Chromans (chemistry, pharmacology)
• Drug Synergism
• Drugs, Chinese Herbal (chemistry)
• Indenes (chemistry, pharmacology)
• Methicillin-Resistant Staphylococcus aureus (drug effects)
• Microbial Sensitivity Tests
• Molecular Structure