Anti-methicillin-resistant Staphylococcus aureus assay of azalomycin F5a and its derivatives.

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.