ABSTRACT
AIM@#To discover anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) microbial natural products or their derivatives.@*METHOD@#Azalomycin F5a (1) was prepared through fermentation of Streptomyces hygroscopicus var. azalomyceticus, and its derivatives were synthesized through hydrocarbylation in hydrocarbyl alcoholic-AcOH (4 : 1) and subsequent demalonylation with 2 mol·L(-1) KOH in MeOH-H2O (7 : 3). Their activities against MRSA ATCC 33592 and three clinical MRSA isolates were evaluated by the agar diffusion and broth microdilution methods.@*RESULTS@#Four demalonylazalomycin F5a derivatives 2 to 5 were synthesized. The anti-MRSA activity assay indicated that compounds 1 to 5 showed remarkable activity against MRSA, and their minimum inhibitory concentrations (MICs) were respectively 3.0-4.0, 0.5-1.0, 0.67-1.0, 0.67-0.83, and 0.5-0.83 μg·mL(-1).@*CONCLUSION@#Azalomycin F5a and the demalonylazalomycin F5a derivatives 2-5 showed remarkable anti-MRSA activity, and the anti-MRSA activities of 2 to 5 were higher than that of 1, while the anti-MRSA activities of 2 to 5 showed no obvious differences. It was also shown that the malonyl monoester group of azalomycin F5a was less important for its anti-MRSA activity.
Subject(s)
Humans , Anti-Bacterial Agents , Chemistry , Pharmacology , Macrolides , Chemistry , Pharmacology , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Molecular Structure , Staphylococcal Infections , Microbiology , Structure-Activity RelationshipABSTRACT
OBJECTIVE: To research the anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activities of azalomycins F5a, F4a and F3a and their potential synergistic anti-MRSA activities combined with other compounds. METHODS: Against a reference strain MRSA ATCC 33592 and eight clinical isolates MRSA 01-08, the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of three main components of azalomycin F were determined by broth microdilution method, and daptomycin was used as positive control. The anti-MRSA effects of them combined with carnosic acid or trimethylhydroquinone were designed with checkerboard method, and determined by broth microdilution method. RESULTS: Their MICs of azalomycins F5a, F4a and F3a against all nine MRSA strains were successively 4-8, 4 and 4-8 μg · mL-1, and all their MBCs were 8-16 μg · mL-1. All the fractional inhibitory concentration indices (FICIs) of them combined with carnosic acid or trimethylhydroquinone were 0.75-1.25 (indifference) or 0.25-0.50 (synergism). CONCLUSION: Three main compounds of azalomycin F have remarkable anti-MRSA activities, and the anti-MRSA effect of azalomycins F5a, F4a or F3a combined with trimethylhydroquinone was synergistic. As new anti-MRSA macrocyclide, azalomycin F is worthy of further research and development.