Synergy of aminoglycoside antibiotics by 3-Benzylchroman derivatives from the Chinese drug Caesalpinia sappan against clinical methicillin-resistant Staphylococcus aureus (MRSA).
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.
Research Center for Natural Medicines, Kunming General Hospital of Chengdu Military Command, Kunming 650032, China. Electronic address: zuoguoying@263.net.
G Y
GY
Zuo
Research Center for Natural Medicines, Kunming General Hospital of Chengdu Military Command, Kunming 650032, China; School of Pharmacy, Guiyang Medical University, Guiyang 550004, China.
Z Q
ZQ
Han
School of Pharmacy, Guiyang Medical University, Guiyang 550004, China.
X Y
XY
Hao
School of Basic Medical Sciences, Yunnan Traditional Chinese Medical College, Kunming 650500, China.
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J
Han
Kunming Institute of Virology of Chengdu Military Command, Kunming 650032, China.
Z S
ZS
Li
Research Center for Natural Medicines, Kunming General Hospital of Chengdu Military Command, Kunming 650032, China.
G C
GC
Wang
D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D002839:Chromans; D004365:Drugs, Chinese Herbal; D007192:Indenes; C522058:sappanone B; C050295:brazilein; C044362:brazilin
Aminoglycoside; Anti-MRSA activity; Bactericidal; Brazilin; Synergy